Eosinophil Response Against Classical and Emerging Respiratory Viruses: COVID-19

Eosinophils were discovered more than 140 years ago. These polymorphonuclear leukocytes have a very active metabolism and contain numerous intracellular secretory granules that enable multiple effects on both health and disease status. Classically, eosinophils have been considered important immune cells in the pathogenesis of inflammatory processes (eg, parasitic helminth infections) and allergic or pulmonary diseases (eg, asthma) and are always associated with a type 2 immune response. Furthermore, in recent years, eosinophils have been linked to the immune response by conferring host protection against fungi, bacteria, and viruses, which they recognize through several molecules, such as toll-like receptors and the retinoic acid–inducible gene 1–like receptor. The immune protection provided by eosinophils is exerted through multiple mechanisms and properties. Eosinophils contain numerous cytoplasmatic granules that release cationic proteins, cytokines, chemokines, and other molecules, all of which contribute to their functioning. In addition to the competence of eosinophils as effector cells, their capabilities as antigen-presenting cells enable them to act in multiple situations, thus promoting diverse aspects of the immune response. This review summarizes various aspects of eosinophil biology, with emphasis on the mechanisms used and roles played by eosinophils in host defence against viral infections and response to vaccines. The review focuses on respiratory viruses, such as the new coronavirus, SARS-CoV-2. (AU)

Los eosinófilos fueron descubiertos hace más de 140 años. Este leucocito polimorfonuclear tiene un metabolismo muy activo y contiene numerosos gránulos secretores intracelulares que le permiten ejercer múltiples funciones tanto en el estado no patológico como en el de la enfermedad. Clásicamente, los eosinófilos se han considerado como importantes células inmunes en la patogénesis de procesos inflamatorios tales como infecciones parasitarias por helmintos y enfermedades alérgicas y/o pulmonares como el asma, las cuales están asociadas a una respuesta inmune tipo 2. Además, en los últimos años, los eosinófilos también han sido relacionados con la respuesta inmunológica que confiere protección al huésped contra hongos, bacterias y virus, reconociéndolos a través de varias moléculas como los receptores tipo Toll (TLR) o los receptores parecidos al gen inducible por ácido retinoico 1 (RIG-1) o RLR. La protección inmune es ejercida a través de los múltiples mecanismos y propiedades características de estas células. Contienen numerosos gránulos citoplasmáticos que liberan proteínas catiónicas, citocinas, quimiocinas y otras moléculas que contribuyen a estas funciones. Además de su competencia como células efectoras, sus capacidades como célula presentadora de antígeno les permite actuar en múltiples situaciones, promoviendo diversos aspectos de la respuesta inmune. En esta revisión se resumen diversos aspectos de la biología de los eosinófilos y, principalmente, se repasan los mecanismos y funciones que desempeñan estas células en la defensa del huésped contra las infecciones por virus, así como la respuesta desencadenada por las vacunas víricas, focalizando la atención en los virus respiratorios como el nuevo coronavirus SARS-CoV-2. (AU)

Mast Cell Tryptase Promotes Inflammatory Bowel Disease-Induced Intestinal Fibrosis.

BACKGROUND: Intestinal fibrosis is the final pathological outcome of chronic intestinal inflammation without specific therapeutic drugs, which leads to ileus and surgical intervention. Intestinal fibrosis is characterized by excessive deposition of extracellular matrix (ECM). The role of mast cells (MCs), which are members of the sentinel immune cell population, is unknown in intestinal fibrosis. METHODS: In this study, we analyzed changes in MCs, tryptase proteins, and ECM components in human fibrotic and control patient intestines. We constructed dextran sodium sulfate-induced intestinal fibrosis models using wild-type mice, MC-reconstituted mice, and MC-deficient mice to explore the role of MCs and tryptase in intestinal fibrosis. The roles and mechanisms of MCs and tryptase on fibroblasts were evaluated using human MCs (HMC-1 and LAD-2), commercial tryptase proteins, human colon fibroblasts (CCD-18Co fibroblasts), the tryptase inhibitor APC366, and the protease-activated receptor-2 (PAR-2) antagonist ENMD-1068. RESULTS: Regardless of whether the colon was a human colon or a mouse colon, the fibrotic intestinal tissue had increased MC infiltration and a higher expression of ECM proteins or genes than that of the control group. The dextran sodium sulfate-induced intestinal fibrosis in MC-deficient mice was alleviated compared with that in wild-type mice. After MC reconstruction in MC-deficient mice, the alleviating effect disappeared. Tryptase, as a content stored in MC granules, was released into fibrotic intestinal tissues in the form of degranulation, resulting in an increased expression of tryptase. Compared with the control group, the tryptase inhibition group (the APC366 group) had reduced intestinal fibrosis. The CCD-18Co fibroblasts, when cocultured with MCs or treated with tryptase proteins, were activated to differentiate into myofibroblasts and secrete more ECM proteins (such as collagen and fibronectin). The underlying mechanism of fibroblast activation by tryptase was the activation of the PAR-2/Akt/mTOR pathway. CONCLUSIONS: We found that MC tryptase promotes inflammatory bowel disease-induced intestinal fibrosis. The underlying mechanism is that tryptase promotes the differentiation of fibroblasts into fibrotic-phenotype myofibroblasts by activating the PAR-2/Akt/ mTOR pathway of fibroblasts.

Recurrent anaphylaxis due to enoxaparin

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Fatal anaphylaxis associated eith the gadolinium-based contrast agent gadoteridol (ProHance)

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Perioperative allergic reactions: Experience in a Flemish referral centre

BACKGROUND: The incidence of perioperative anaphylactic reactions is overall estimated to be 1 per 10,000-20,000 anaesthetic procedures. We performed a retrospective analysis of patients referred to a University Allergy Centre in Belgium with the suspicion of an allergic reaction during or shortly after general anaesthesia. OBJECTIVES: Our aim was to assess the causes of perioperative allergic reactions, to evaluate cross-reactivity among neuromuscular blocking agents (NMBA) and to analyze the diagnostic relevance of tryptase levels in the discrimination between IgE and non-IgE-mediated reactions. METHODS: A total of 119 patients, referred from 2007 to 2011 were included. The diagnostic protocol consisted in case history, serum tryptase measurements, immunoassays and skin tests. RESULTS: A diagnosis of IgE-mediated reaction was established in 76 cases (63.9%). The most common agents were NMBA (61.8%), antibiotics (14.5%), latex (9.2%) and chlorhexidine (5.2%). Rocuronium was the most frequently causative NMBA (48.9%). Vecuronium cross-reactivity was established by skin testing in 47.6% of cases. Cisatracurium was the NMBA most frequently tolerated (cross-reaction in 13.9%). In 23.4% of NMBA allergic patients, the reaction occurred on the first exposure. Most IgE-mediated reactions occurred during the induction phase (72.4%). Latex-induced reactions occurred mainly during maintenance and recovery phases (71.4%; p < 0.02). Mean tryptase values were significantly higher in patients with IgE-mediated reactions (p = 0.0001), than in those with no identified cause. CONCLUSIONS: NMBA, antibiotics, latex and chlorhexidine were the main culprits of IgE-mediated perioperative reactions. Uncertainties remain concerning the specificity and sensitivity of skin testing. Tryptase assays can be useful in the discrimination of IgE and non-IgE-mediated reactions

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Baseline Tryptase Levels Are Related to Age, Total IgE, and Anti-rPru p 3 IgE Levels in Peach-Allergic Patients

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Anafilaxia perioperatoria / No disponible

La anafilaxia perioperatoria puede ser una un cuadro clínico que amenaza la vida del paciente, producido por los fármacos o sustancias usadas en la anestesia. Después de una anafilaxia, debe realizarse un estudio alergológico para identificar el agente responsable y prevenir recurrencias. La incidencia global es de 1 entre 10.000-20.000 anestesias. Los agentes más frecuentemente implicados son los bloqueantes neuromusculares, látex y antibióticos. El diagnóstico inicial es mediante la clínica. En el tratamiento es esencial la adrenalina(AU)

Perioperative anaphylaxis may be a life threatening clinical condition and is typically a results of drugs used for anesthesia. After anaphylaxis, allergologic assessment is essential to identify the offending agent and prevent recurrences. The overall incidence is estimated at 1 in 10,000-20,000 anesthetic procedures. The most commonly involved agents are neuromuscular blocking agents, latex and antibiotics. The initial diagnosis is presumptive, including clinical signs. Adrenalin is the treatment of choice(AU)