RESUMEN
Tryptase is currently the main mast cell biomarker available in medical practice. Tryptase determination is a quantitative test performed in serum or plasma for the diagnosis, stratification, and follow-up of mast cell-related conditions. The continuous secretion of monomeric α and ß protryptases forms the baseline tryptase level. Transient, activation-induced release of tryptase is known as acute tryptase. Because mast cells are tissue-resident cells, the detection of an acute tryptase release in the bloodstream is protracted, with a delay of 15 to 20 minutes after the onset of symptoms and a peak at approximately 1 hour. Constitutive release of tryptase is a marker of mast cell number and activity status, whereas transient release of mature tryptase is a marker of mast cell degranulation. Although consensual as a concept, the application of this statement in clinical practice has only been clarified since 2020. For baseline tryptase to be used as a biomarker, reference values need to be established. In contrast, defining a transient increase using acute tryptase can only be achieved as a function of the baseline status.
Asunto(s)
Hipersensibilidad Inmediata , Mastocitos , Triptasas , Humanos , Anafilaxia/diagnóstico , Biomarcadores/sangre , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/inmunología , Mastocitos/enzimología , Mastocitos/inmunología , Triptasas/sangre , Triptasas/inmunologíaRESUMEN
PURPOSE OF REVIEW: Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase in Western populations. It is a risk factor for severe anaphylaxis among individuals with venom allergy and an established modifier of anaphylaxis and mast cell mediator-associated symptoms among patients with systemic mastocytosis. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HαT is the first step in identifying optimal medical management and targets for novel therapeutics. RECENT FINDINGS: HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/ß-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.
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Anafilaxia , Mastocitosis , Triptasas , Anafilaxia/sangre , Anafilaxia/genética , Anafilaxia/inmunología , Genotipo , Humanos , Mastocitos/inmunología , Mastocitosis/sangre , Mastocitosis/genética , Mastocitosis/inmunología , Fenotipo , Triptasas/sangre , Triptasas/genética , Triptasas/inmunologíaRESUMEN
BACKGROUND: Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom-triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL). OBJECTIVE: Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy. METHODS: We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR. RESULTS: In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% [24 of 132] vs 1.8% in patients with lower grades [4 of 88 with grade III and 0 of 131 with other grades]; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% [14 of 24] vs 34.3% [37 of 108]; P = .03) and absence of skin symptoms (41.7% [10 of 24] vs 15.7% [17 of 108]; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 [95% CI = 3.75-36.14]; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% [15 of 23]) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA. CONCLUSION: These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone.
Asunto(s)
Anafilaxia , Venenos de Artrópodos/toxicidad , Pruebas Genéticas , Mastocitos/inmunología , Mastocitosis Sistémica , Mutación Missense , Proteínas Proto-Oncogénicas c-kit , Triptasas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Anafilaxia/genética , Anafilaxia/inmunología , Femenino , Humanos , Masculino , Mastocitosis Sistémica/genética , Mastocitosis Sistémica/inmunología , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/inmunología , Triptasas/genéticaRESUMEN
Murine mast cells (MCs) contain two lineages: inducible bone marrow-derived mucosal MCs (MMCs) and constitutive embryonic-derived connective tissue MCs (CTMCs). Here, we use RNA sequencing, flow cytometry, and genetic deletion in two allergic lung inflammation models to define these two lineages. We found that inducible MCs, marked by ß7 integrin expression, are highly distinct from airway CTMCs at rest and during inflammation and unaffected by targeted CTMC deletion. ß7High MCs expand and mature during lung inflammation as part of a TGF-ß-inducible transcriptional program that includes the MMC-associated proteases Mcpt1 and Mcpt2, the basophil-associated protease Mcpt8, granule components, and the epithelial-binding αE integrin. In vitro studies using bone marrow-derived MCs (BMMCs) identified a requirement for SCF in this this TGF-ß-mediated development and found that epithelial cells directly elicit TGF-ß-dependent BMMC up-regulation of mMCP-1 and αE integrin. Thus, our findings characterize the expansion of a distinct inducible MC subset in C57BL/6 mice and highlight the potential for epithelium to direct MMC development.
Asunto(s)
Asma/inmunología , Células de la Médula Ósea/inmunología , Linaje de la Célula/inmunología , Mastocitos/inmunología , Mucosa Respiratoria/inmunología , Animales , Asma/embriología , Asma/genética , Asma/patología , Células de la Médula Ósea/patología , Linaje de la Célula/genética , Cadenas beta de Integrinas/genética , Cadenas beta de Integrinas/inmunología , Mastocitos/patología , Ratones , Ratones Transgénicos , Mucosa Respiratoria/embriología , Mucosa Respiratoria/patología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunología , Triptasas/genética , Triptasas/inmunologíaRESUMEN
OBJECTIVE: This study aims to investigate the role of protease-activated receptor (PAR) 2 and mast cell (MC) tryptase in LPS-induced lung inflammation and neutrophil recruitment in the lungs of C57BL/6 mice. METHODS: C57BL/6 mice were pretreated with the PAR2 antagonist ENMD-1068, compound 48/80 or aprotinin prior to intranasal instillation of MC tryptase or LPS. Blood leukocytes, C-X-C motif chemokine ligand (CXCL) 1 production leukocytes recovered from bronchoalveolar lavage fluid (BALF), and histopathological analysis of the lung were evaluated 4 h later. Furthermore, we performed experiments to determine intracellular calcium signaling in RAW 264.7 cells stimulated with LPS in the presence or absence of a protease inhibitor cocktail or ENMD-1068 and evaluated PAR2 expression in the lungs of LPS-treated mice. RESULTS: Pharmacological blockade of PAR2 or inhibition of proteases reduced neutrophils recovered in BALF and LPS-induced calcium signaling. PAR2 blockade impaired LPS-induced lung inflammation, PAR2 expression in the lung and CXCL1 release in BALF, and increased circulating blood neutrophils. Intranasal instillation of MC tryptase increased the number of neutrophils recovered in BALF, and MC depletion with compound 48/80 impaired LPS-induced neutrophil migration. CONCLUSION: Our study provides, for the first time, evidence of a pivotal role for MCs and MC tryptase in neutrophil migration, lung inflammation and macrophage activation triggered by LPS, by a mechanism dependent on PAR2 activation.
Asunto(s)
Mastocitos/inmunología , Infiltración Neutrófila , Neumonía/inmunología , Receptor PAR-2/inmunología , Triptasas/inmunología , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Señalización del Calcio , Quimiocina CXCL1/inmunología , Femenino , Lipopolisacáridos , Pulmón/inmunología , Pulmón/patología , Activación de Macrófagos , Ratones , Ratones Endogámicos C57BL , Piperazinas/farmacología , Neumonía/inducido químicamente , Neumonía/patología , Células RAW 264.7 , Receptor PAR-2/antagonistas & inhibidoresRESUMEN
Objective: Multiple proteinases are present in the synovial fluid (SF) of an arthritic joint. We aimed to identify inflammatory cell populations present in psoriatic arthritis (PsA) SF compared to osteoarthritis (OA) and rheumatoid arthritis (RA), identify their proteinase-activated receptor 2 (PAR2) signaling function and characterize potentially active SF serine proteinases that may be PAR2 activators. Methods: Flow cytometry was used to characterize SF cells from PsA, RA, OA patients; PsA SF cells were further characterized by single cell 3'-RNA-sequencing. Active serine proteinases were identified through cleavage of fluorogenic trypsin- and chymotrypsin-like substrates, activity-based probe analysis and proteomics. Fluo-4 AM was used to monitor intracellular calcium cell signaling. Cytokine expression was evaluated using a multiplex Luminex panel. Results: PsA SF cells were dominated by monocytes/macrophages, which consisted of three populations representing classical, non-classical and intermediate cells. The classical monocytes/macrophages were reduced in PsA compared to OA/RA, whilst the intermediate population was increased. PAR2 was elevated in OA vs. PsA/RA SF monocytes/macrophages, particularly in the intermediate population. PAR2 expression and signaling in primary PsA monocytes/macrophages significantly impacted the production of monocyte chemoattractant protein-1 (MCP-1). Trypsin-like serine proteinase activity was elevated in PsA and RA SF compared to OA, while chymotrypsin-like activity was elevated in RA compared to PsA. Tryptase-6 was identified as an active serine proteinase in SF that could trigger calcium signaling partially via PAR2. Conclusion: PAR2 and its activating proteinases, including tryptase-6, can be important mediators of inflammation in PsA. Components within this proteinase-receptor axis may represent novel therapeutic targets.
Asunto(s)
Artritis Psoriásica/inmunología , Señalización del Calcio/inmunología , Macrófagos/inmunología , Receptor PAR-2/inmunología , Triptasas/inmunología , Artritis Psoriásica/patología , Femenino , Humanos , Macrófagos/patología , MasculinoRESUMEN
Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active ß-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human ß-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a ß-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/terapia , Mastocitos/enzimología , Mastocitos/inmunología , Triptasas/antagonistas & inhibidores , Triptasas/inmunología , Adolescente , Regulación Alostérica/inmunología , Animales , Línea Celular , Femenino , Humanos , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , ConejosRESUMEN
BACKGROUND: Mast cells are involved in the host immune response controlling infection with the non-invasive intestinal protozoan parasite Giardia intestinalis. Experimental infections in rodents with G. intestinalis showed increased intestinal expression of mucosal and connective mast cell specific proteases suggesting that both mucosal and connective tissue mast cells are recruited and activated during infection. During infection Giardia excretory-secretory proteins (ESPs) with immunomodulatory capacity are released. However, studies investigating potential interactions between Giardia ESPs and the connective tissue mast cell specific serine proteases, i.e. human chymase and mouse mast cell protease (mMCP)-4 and, human and mouse tryptase (mMCP-6) remain scarce. RESULTS: We first investigated if soluble Giardia proteins (sGPs), which over-lap extensively in protein content with ESP fractions, from the isolates GS, WB and H3, could induce mast cell activation. sGPs induced a minor activation of bone marrow derived mucosal-like mast cells, as indicated by increased IL-6 secretion and no degranulation. Furthermore, sGPs were highly resistant to degradation by human tryptase while human chymase degraded a 65 kDa sGP and, wild-type mouse ear tissue extracts degraded several protein bands in the 10 to 75 kDa range. In striking contrast, sGPs and ESPs were found to increase the enzymatic activity of human and mouse tryptase and to reduce the activity of human and mouse chymase. CONCLUSION: Our finding suggests that Giardia ssp. via enhancement or reduction of mast cell protease activity may modulate mast cell-driven intestinal immune responses. ESP-mediated modulation of the mast cell specific proteases may also increase degradation of tight junctions, which may be beneficial for Giardia ssp. during infection.
Asunto(s)
Quimasas/inmunología , Giardia/inmunología , Giardiasis/inmunología , Mastocitos/inmunología , Mastocitos/parasitología , Triptasas/inmunología , Animales , Endopeptidasas/inmunología , Giardiasis/parasitología , Humanos , Intestinos/inmunología , Intestinos/parasitología , Ratones , Ratones Endogámicos C57BL , Proteolisis , Serina Endopeptidasas/inmunologíaRESUMEN
PURPOSE OF REVIEW: To recognize the relevance of serum tryptase measurement as a useful tool for the diagnosis of allergic diseases and mast cell disorders. RECENT FINDINGS: Recent data on the role of mast cells and tryptase in allergic and other diseases provide new understanding into the mechanisms and causes of anaphylaxis. SUMMARY: Measurement of transiently elevated tryptase levels shortly after a severe reaction can help elucidate mechanism behind the reaction in identifying mast cell activation. Hymenoptera venom allergy represents an important cause of morbidity and mortality worldwide. Venom allergy is a typical IgE-mediated reaction because of sensitization to one or more allergens of the venom, and accounts for 1.5-34% of all cases of anaphylaxis. There is a preferential association between insect venom allergy and mastocytosis. The diagnosis of a clonal mast cell disease leads to therapeutic consequences concerning the treatment of venom allergy. In conclusion, baseline tryptase levels support the clinical diagnosis of anaphylaxis and mast cell disorders, determine venom immunotherapy treatment and are relevant in deciding on lifelong treatment.
Asunto(s)
Anafilaxia , Mordeduras y Picaduras de Insectos , Mastocitos , Mastocitosis , Triptasas , Anafilaxia/sangre , Anafilaxia/inmunología , Anafilaxia/terapia , Animales , Venenos de Artrópodos/inmunología , Venenos de Artrópodos/toxicidad , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Mordeduras y Picaduras de Insectos/sangre , Mordeduras y Picaduras de Insectos/inmunología , Mordeduras y Picaduras de Insectos/terapia , Insectos , Mastocitos/inmunología , Mastocitos/metabolismo , Mastocitosis/sangre , Mastocitosis/inmunología , Mastocitosis/terapia , Triptasas/sangre , Triptasas/inmunologíaRESUMEN
INTRODUCTION: A reduced number of interstitial Cajal-like cells (ICLCs) in the gallbladder have been proposed to play a role in the pathogenesis of cholelithiasis. Therefore, this prospective study was conducted to investigate the relationship between gallbladder contractility and the number of gallbladder ICLCs in patients with cholelithiasis. MATERIAL AND METHODS: Patients admitted to the Department of Hepatobiliary Surgery for cholecystectomy were divided into the cholelithiasis (n = 18) and non-cholelithiasis (n = 8) groups based on their clinical data. Patients' clinical data were collected on admission, and B-mode ultrasonography was performed to assess their gallbladder contractility. The resected gallbladder specimens were fixed, paraffin sections mounted on slides, and the immunofluorescence staining with the anti-human CD-117 and anti-human tryptase antibodies was performed to identify ICLSs and mast cells, respectively. The number of ICLCs was counted in 10 high-power fields (HPFs) randomly. RESULTS: Independent sample t-tests revealed differences between the cholelithiasis and non-cholelithiasis groups in the number of ICLCs (mean ± standard deviation: 88.61 ± 28.22 vs. 115.89 ± 27.87 per HPFs, P = 0.032) and gallbladder contractility (43.94% ± 18.50% vs. 61.00% ± 20.50%, P = 0.046). Pearson and Spearman cor-relation analyses revealed no significant correlation between the number of ICLCs and gallbladder contractility. CONCLUSION: The results suggest that the number of gallbladder ICLCs in the wall of the gallbladder of patients with or without cholelithiasis is not a decisive factor affecting gallbladder contractility.
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Colelitiasis/fisiopatología , Vaciamiento Vesicular/fisiología , Vesícula Biliar/citología , Vesícula Biliar/fisiología , Telocitos/citología , Adulto , Anciano , Animales , Anticuerpos/inmunología , Recuento de Células , Colelitiasis/patología , Femenino , Vesícula Biliar/patología , Cabras , Humanos , Masculino , Ratones , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Proto-Oncogénicas c-kit/inmunología , Conejos , Telocitos/patología , Triptasas/inmunologíaRESUMEN
Patients with clonal mast cell activation syndromes (MCAS) including cutaneous and systemic mastocytosis (SM) may present with symptoms of mast cell activation, but in addition can have organ damage from the local effects of tissue infiltration by clonal mast cells. Patients with nonclonal MCAS may have chronic or episodic mast cell activation symptoms with an increase in serum tryptase and/or urinary metabolites of histamine, prostaglandin D2, and leukotrienes. Symptoms of MCAS and SM can be managed by blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade), inhibition of mediator synthesis (aspirin, zileuton), mediator release (sodium cromolyn), anti-IgE therapy, or a combination of these approaches. Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids. Patients with clonal mast cell syndromes may need a reduction in the number of mast cells to prevent severe symptoms including anaphylaxis and/or progression to aggressive diseases.
Asunto(s)
Antialérgicos/uso terapéutico , Glucocorticoides/uso terapéutico , Antagonistas de los Receptores Histamínicos/uso terapéutico , Antagonistas de Leucotrieno/uso terapéutico , Mastocitosis/tratamiento farmacológico , Antiasmáticos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Cromolin Sódico/uso terapéutico , Manejo de la Enfermedad , Histamina/inmunología , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Hidroxiurea/análogos & derivados , Hidroxiurea/uso terapéutico , Interleucina-6/inmunología , Interleucina-6/metabolismo , Leucotrieno E4/inmunología , Leucotrieno E4/metabolismo , Mastocitosis/inmunología , Mastocitosis/metabolismo , Omalizumab/uso terapéutico , Prostaglandina D2/inmunología , Prostaglandina D2/metabolismo , Triptasas/inmunología , Triptasas/metabolismoRESUMEN
BACKGROUND: Anaphylaxis is recognized mainly through clinical criteria, which may lack specificity or relevance in the perioperative setting. The transient increase in serum tryptase has been proposed since 1989 as a diagnostic tool. Sampling for well-defined acute and baseline determinations has been recommended. We assessed the performance of four proposed algorithms with tightly controlled time frames for tryptase sampling, their robustness with inadequate sampling times, and the possible use of mature tryptase determination. METHODS: A retrospective study was performed on 102 adult patients from the Aix-Marseille University Hospitals who had experienced a perioperative hypersensitivity reaction clinically suggesting anaphylaxis. EAACI and ICON criteria were used to diagnose anaphylaxis. Mature and total serum tryptase levels were measured. RESULTS: Based on EAACI guidelines, clinical diagnostic criteria for anaphylaxis were found in 76 patients and lacking in 26. The most effective algorithm was the international consensus recommendation of 2012 that acute total tryptase levels should be greater than ([1.2×baseline tryptase] + 2] µg/L to be considered a clinically significant rise. In our cohort, this algorithm achieved 94% positive predictive value (PPV), 53% negative predictive value (NPV), 75% sensitivity, 86% specificity, and a Youden's index value of 0.61. A detectable acute mature tryptase level showed lower sensitivity, particularly in patients with acute total tryptase levels lower than 16 µg/L. Acute tryptase levels varied as a function of the clinical severity of anaphylaxis. CONCLUSION: Total tryptase levels in serum discriminated between nonanaphylactic and anaphylactic events in a perioperative setting when acute and baseline levels were collected and analyzed by the consensus algorithm.
Asunto(s)
Anafilaxia/sangre , Anafilaxia/diagnóstico , Periodo Perioperatorio , Triptasas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Biomarcadores/sangre , Consenso , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Pruebas Serológicas , Triptasas/inmunología , Adulto JovenRESUMEN
PURPOSE OF THE STUDY This study deals with the possibilities and application of immunohistochemical methods to detect mast and dendritic cells in periprosthetic tissues in patients with aseptically loosened total joint replacements of the knee and hip. The purpose of the study was to quantify and characterize the distribution of mast and dendritic cells in the examined samples and to study the statistically significant relations between the aforementioned cell populations and selected parameters characterizing the patients, implants or tissue response. Based on the proved findings, a possible relation between mast and dendritic cells and histomorphological patterns of aseptic loosening and the benefit of the applied immunohistochemical methods was evaluated. MATERIAL AND METHODS Periprosthetic tissues from a total of 31 patients (17 patients after a revision surgery of hip prosthesis, 14 patients after a revision surgery of knee prosthesis) were examined. The collected samples were processed according to the standard protocol for the purposes of histological and immunochemical examination. Antibodies against tryptase and CD117 were used for immunohistochemical detection of mast cells. Dendritic cells were detected by means of S100 and CD1a antibodies. Quantification of both the cell populations was carried out by optical microscopy in 20 high power fields at 400-times magnification. From among the applied methods we picked the more sensitive one for statistical evaluation. It was tryptase in the case of mast cells and S100 in the case of dendritic cells. RESULTS Mast and dendritic cells were mostly distributed dispersively in periprosthetic tissues; however, they also occurred in groups perivasally or near necrotic parts. The examined samples showed the presence of 60 mast cells and 50 dendritic cells on average. The increased density of mast and dendritic cells was associated with polypously formed pseudosynovium and cement fixation of prostheses; this relation was statistically significant. It was impossible to prove the correlation between the quantity of the observed cell populations and the nature and the number of the observed particles because wear particles were present dispersely in all the samples. Another statistically significant relation to the type of material or implant fixation or other examined histomorphological patterns was not proved. A strong density of mast cells with a minimum presence of dendritic cells was observed in the control patient group. DISCUSSION The differences in density of S100 positive dendritic cells between the control and examined group of patients can be caused by the activation of dendritic cells by exogenous or endogenous pathways of immune processes going on after the implantation of endoprosthesis. The statistically significant interrelation of mast cells, polypously formed pseudosynovium and cement wear particles can be explained at least in part as a tissue reaction induced by cement particles. CONCLUSIONS We proved the presence of two immunologically significant cell populations in periprosthetic tissues. The said findings indicate a conclusion of significant functional participation of mast and dendritic cells in pathogenesis of aseptic loosening and periprosthetic osteolysis. Nevertheless, this will have to be proved in another way and with the use of another method. Key words:dendritic cells, mast cells, aseptic loosening, total joint replacement, immune reaction, adverse reaction.
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Células Dendríticas/inmunología , Prótesis de Cadera/microbiología , Prótesis de la Rodilla/microbiología , Mastocitos/inmunología , Falla de Prótesis/efectos adversos , Antígenos CD1/inmunología , Células Dendríticas/ultraestructura , Articulación de la Cadera/microbiología , Articulación de la Cadera/patología , Articulación de la Cadera/cirugía , Prótesis de Cadera/efectos adversos , Humanos , Articulación de la Rodilla/microbiología , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Prótesis de la Rodilla/efectos adversos , Mastocitos/ultraestructura , Microscopía/instrumentación , Proteínas Proto-Oncogénicas c-kit/inmunología , Reoperación/métodos , Proteínas S100/inmunología , Triptasas/inmunologíaRESUMEN
Infections with helminth parasites are controlled by a concerted action of innate and adaptive effector cells in the frame of a type 2 immune response. Basophils are innate effector cells that may also contribute to the initiation and amplification of adaptive immune responses. Here, we use constitutively basophil-deficient Mcpt8-Cre mice to analyze the impact of basophils during initiation and execution of the protective type 2 responses to both, a primary infection and a challenge infection of immune mice with the helminth parasite Strongyloides ratti. Basophil numbers expanded during parasite infection in blood and mesenteric lymph nodes. Basophil deficiency significantly elevated intestinal parasite numbers and fecal release of eggs and larvae during a primary infection. However, basophils were neither required for the initiation of a S. ratti-specific cellular and humoral type 2 immune response nor for the efficient protection against a challenge infection. Production of Th2 cytokines, IgG1 and IgE as well as mast cell activation were not reduced in basophil-deficient Mcpt8-Cre mice compared to basophil-competent Mcpt8-WT littermates. In addition, a challenge infection of immune basophil-deficient and WT mice resulted in a comparable reduction of tissue migrating larvae, parasites in the intestine and fecal release of eggs and L1 compared to mice infected for the first time. We have shown previously that S. ratti infection induced expansion of Foxp3+ regulatory T cells that interfered with efficient parasite expulsion. Here we show that depletion of regulatory T cells reduced intestinal parasite burden also in absence of basophils. Thus basophils were not targeted specifically by S. ratti-mediated immune evasive mechanisms. Our collective data rather suggests that basophils are non-redundant innate effector cells during murine Strongyloides infections that contribute to the early control of intestinal parasite burden.
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Inmunidad Adaptativa , Basófilos/inmunología , Parasitosis Intestinales/inmunología , Strongyloides ratti/fisiología , Estrongiloidiasis/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Citocinas/inmunología , Femenino , Humanos , Inmunidad Humoral , Inmunoglobulina E/inmunología , Parasitosis Intestinales/parasitología , Masculino , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Strongyloides ratti/genética , Estrongiloidiasis/parasitología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Triptasas/genética , Triptasas/inmunologíaRESUMEN
PURPOSE OF REVIEW: The aim of the review is to describe the different clinical pictures of anaphylaxis (phenotypes), in relation to the underlying mechanisms and potential biomarkers, to describe anaphylaxis endotypes. This may aid in achieving a better understanding, management and outcomes of such severe reactions. RECENT FINDINGS: Different anaphylaxis phenotypes have been outlined, ranging from the classical type-I-like to those suggestive of cytokine-storm-like or complement-mediated reactions. Underlying mechanisms differ and biomarkers of cells and systems involved are being identified (tryptase, IL-6, bradykinin etc.) SUMMARY: Identifying specific phenotypes/endotypes will allow the application of precision medicine in patients with anaphylaxis, providing insights to the most appropriate approach in each case.
Asunto(s)
Anafilaxia/inmunología , Biomarcadores/metabolismo , Activación de Complemento/inmunología , Citocinas/inmunología , Fenotipo , Anafilaxia/metabolismo , Basófilos/inmunología , Bradiquinina/inmunología , Bradiquinina/metabolismo , Carboxipeptidasas A/inmunología , Carboxipeptidasas A/metabolismo , Quimasas/inmunología , Quimasas/metabolismo , Citocinas/metabolismo , Histamina/inmunología , Histamina/metabolismo , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Interleucina-6/inmunología , Interleucina-6/metabolismo , Mastocitos/inmunología , Factor de Activación Plaquetaria/inmunología , Factor de Activación Plaquetaria/metabolismo , Medicina de Precisión , Triptasas/inmunología , Triptasas/metabolismoRESUMEN
Tuberculosis is one of the leading causes of human morbidity and mortality. Mycobacterium tuberculosis (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections via inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection.
Asunto(s)
Proteínas Bacterianas/inmunología , Catalasa/inmunología , Trampas Extracelulares/inmunología , Inmunidad Innata , Mastocitos/inmunología , Mycobacterium tuberculosis/inmunología , Animales , Proteínas Bacterianas/metabolismo , Catalasa/metabolismo , Línea Celular , Trampas Extracelulares/metabolismo , Humanos , Mastocitos/enzimología , Ratones , Mycobacterium tuberculosis/enzimología , Triptasas/inmunología , Triptasas/metabolismo , Tuberculosis/enzimología , Tuberculosis/inmunología , Tuberculosis/patologíaRESUMEN
Odontogenic lesions differ in their rate of recurrence and aggressiveness. This study aimed to evaluate the presence of myofibroblasts and mast cells in odontogenic lesions. Sample consisted of 20 cases each of dentigerous cysts, odontogenic keratocysts, and solid ameloblastomas. Histologic sections were submitted to immunohistochemistry using anti-α-smooth muscle actin and anti-tryptase antibodies. Myofibroblasts and mast cells were counted at ×400 magnification in 5 and 10 fields, respectively. Myofibroblasts were more frequent in ameloblastomas (24.41), followed by odontogenic keratocysts (16.21) and dentigerous cysts (11.85; P=.002). Granulated and degranulated mast cells were more frequent in dentigerous cysts (7.88 and 8.96, respectively), followed by odontogenic keratocysts (6.53 and 7.08) and ameloblastomas (5.21 and 1.88). The difference was only significant for degranulated mast cells (P<.05). Analysis of the correlation between myofibroblasts and mast cells (granulated and degranulated) revealed a moderate positive correlation only in ameloblastomas (R=0.621, P=.003). Probably, myofibroblasts are related to the biological behavior of the odontogenic lesions studied, particularly their aggressiveness. On the other hand, mast cells seem to be associated with inflammatory processes, which are more frequent in cystic lesions than in benign neoplasms. In addition, mast cells may induce the differentiation of fibroblasts into myofibroblasts, thus increasing the number of the latter.
Asunto(s)
Ameloblastoma/patología , Mastocitos/patología , Miofibroblastos/patología , Quistes Odontogénicos/patología , Actinas/inmunología , Quiste Dentígero/patología , Humanos , Inmunohistoquímica , Triptasas/inmunologíaRESUMEN
Mast cells are haematopoietic cells that arise from pluripotent precursors of the bone marrow. They play immunomodulatory roles in both health and disease. When appropriately activated, mast cells undergo degranulation, and preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on various inflammatory settings are closely associated with the enzymatic characteristics of tryptase, the main granule compound of mast cells. Tryptase degranulation is often linked with the development of an immune response, allergy, inflammation, and remodelling of tissue architecture. Tryptase also represents an informative diagnostic marker of certain diseases and a prospective target for pharmacotherapy. In this review, we discuss the current knowledge about mast cell tryptase as one of the mast cell secretome proteases. The main points of the reviewed publications are highlighted with our microscopic images of mast cell tryptases visualized using immunohistochemical staining.
Asunto(s)
Mastocitos/enzimología , Triptasas/metabolismo , Animales , Humanos , Inmunohistoquímica , Inflamación/metabolismo , Mastocitos/citología , Mastocitos/metabolismo , Triptasas/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: Serum tryptase (ST) decreases during long-term venom immunotherapy (VIT). ST also exhibits a circadian variation, with a small decrease after sting challenge. Both findings have been related to successful VIT. Objective: To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likelihood of future systemic adverse reactions (SARs) during treatment. METHODS: We prospectively studied patients who underwent cluster VIT, which was continued for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patient groups (with and without SAR) were analyzed. RESULTS: A total of 160 courses of VIT were administered to 150 patients. The median baseline ST value was 4.3 µg/L. A total of 25 courses (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, the post-IT tryptase value was higher than the pre-IT tryptase level; the median increment was 19% in these patients. We found a significant association between the increase in ST on the first day of VIT and future SARs (risk ratio, 7.6). This elevation was independent of the scheduled VIT day, severity of the SAR, and baseline ST value. CONCLUSIONS: A slight increase in tryptase on the first day of VIT is an independent variable that is strongly related to a high risk of future SAR. This simple biomarker could improve patient safety.