Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Gene ; 761: 145036, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777525

RESUMO

Lupinus albus γ-conglutin is proposed to positively affect glucose metabolism through inhibition of hepatic glucose production and insulin-mimetic activity; however, the action mechanism is not entirely known. Besides, most studies had focused on its effect on molecular targets directly related to glucose metabolism, and few studies have investigated how γ-conglutin may affect the liver gene expression or if it plays a role in other metabolic processes. Therefore, we investigated the influence of γ-conglutin on the liver transcriptome of streptozotocin-induced diabetic rats using DNA microarrays, ontological analyses, and quantitative PCR. Of the 22,000 genes evaluated, 803 and 173 were downregulated and upregulated, respectively. The ontological analyses of the differentially expressed genes revealed that among others, the mitochondria, microtubules, cytoskeleton, and oxidoreductase activity terms were enriched, implying a possible role of γ-conglutin on autophagy. To corroborate the microarray results, we selected and quantified, by PCR, the expression of two genes associated with autophagy (Atg7 and Snx18) and found their expression augmented two and threefold, respectively; indicating a higher autophagy activity in animals treated with γ-conglutin. Although complementary studies are required, our findings indicate for the first time that the hypoglycaemic effects of γ-conglutin may involve an autophagy induction mechanism, a pivotal process for the preservation of cell physiology and glucose homeostasis.


Assuntos
Colectinas/farmacologia , Lupinus/metabolismo , Soroglobulinas/farmacologia , Transcriptoma/genética , Animais , Glicemia/metabolismo , Colectinas/metabolismo , Colectinas/fisiologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Fígado/metabolismo , Fígado/patologia , Lupinus/genética , Masculino , Proteínas de Plantas/genética , Ratos , Ratos Wistar , Sementes/metabolismo , Soroglobulinas/metabolismo , Soroglobulinas/fisiologia
2.
Immunobiology ; 221(10): 1058-67, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27377710

RESUMO

Both the complement system and collectins play important roles in our innate immune system. The collectins, which are characterized by their inclusion of a collagen-like region and a calcium-dependent carbohydrate recognition domain, are pattern recognition molecules and include the well characterized proteins mannan-binding lectin (MBL) and the surfactant proteins SP-A/-D. Collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1) and collectin placenta 1 (CL-P1) are the most recently discovered collectins. Although their function is still under investigation, accumulating information suggests that CL-L1, CL-K1 and CL-P1 play important roles in host defense by recognizing a variety of microorganisms and interacting with effector proteins, including complement components. The recent establishment of the existence of CL-K1 in the circulation in form of heteromeric complexes with CL-L1 (known as CL-LK) and its activation of the lectin pathway via MASPs, drew new attention in the complement biology, which was further strengthened by the observed interactions between CL-P1 and CRP-C1q-factor H or properdin. Deficiency of either CL-K1 or MASP-3 has been demonstrated in 3MC syndrome patients with developmental abnormalities, showing that lectin pathway components, regulation and/or activation are essential during the embryonic development; another feature that they most likely share CL-P1. Herein, we discuss the recent characteristics and roles of the collectins CL-L1, CL-K1 and CL-P1 in the complement system, in innate immunity and their possible association with disease development and pathogenesis.


Assuntos
Colectinas/fisiologia , Ativação do Complemento , Proteínas do Sistema Complemento/fisiologia , Imunidade Inata , Animais , Colectinas/química , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , Ligantes , Família Multigênica , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Polimorfismo Genético , Relação Estrutura-Atividade
3.
Biochim Biophys Acta ; 1860(6): 1118-28, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26922829

RESUMO

BACKGROUND: C-reactive protein (CRP) is a plasma pentraxin family protein that is massively induced as part of the innate immune response to infection and tissue injury. CRP and other pentraxin proteins can activate a complement pathway through C1q, collectins, or on microbe surfaces. It has been found that a lectin-like oxidized LDL receptor 1 (LOX-1), which is an endothelial scavenger receptor (SR) having a C-type lectin-like domain, interacts with CRP to activate the complement pathway using C1q. However it remains elusive whether other lectins or SRs are involved in CRP-mediated complement activation and the downstream effect of the complement activation is also unknown. METHODS: We prepared CHO/ldlA7 cells expressing collectin placenta-1 (CL-P1) and studied the interaction of CRP with cells. We further used ELISA for testing binding between proteins. We tested for C3 fragment deposition and terminal complement complex (TCC) formation on HEK293 cells expressing CL-P1. RESULTS: Here, we demonstrated that CL-P1 bound CRP in a charge dependent manner and the interaction of CRP with CL-P1 mediated a classical complement activation pathway through C1q and additionally drove an amplification pathway using properdin. However, CRP also recruits complement factor H (CFH) on CL-P1 expressing cell surfaces, to inhibit the formation of a terminal complement complex in normal complement serum conditions. GENERAL SIGNIFICANCE: The interaction of collectin CL-P1 with CFH might be key for preventing attack on "self" as a result of complement activation induced by the CL-P1 and CRP interaction.


Assuntos
Proteína C-Reativa/química , Colectinas/química , Ativação do Complemento , Receptores Depuradores/química , Animais , Proteína C-Reativa/fisiologia , Células CHO , Colectinas/fisiologia , Fator H do Complemento/química , Cricetulus , Células HEK293 , Humanos , Receptores Depuradores/fisiologia
4.
Indian J Exp Biol ; 53(11): 691-700, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26669011

RESUMO

Aspergillus fumigatus, a ubiquitous fungus, causes a wide spectrum of clinical conditions ranging from allergic to invasive aspergillosis depending upon the hosts' immune status. Several animal models have been generated to mimic the human clinical conditions in allergic and invasive aspergillosis. The onset, duration and severity of the disease developed in models varied depending on the animal strain/fungal isolate, quantity and mode of administration of fungal antigens/spores, duration of the treatment, and type of immunosuppressive agent used. These models provide insight into host and pathogen factors and prove to be useful for evaluation of diagnostic markers and effective therapies. A series of studies established the protective role of collectins in murine models of Allergic Bronchopulmonary Aspergillosis and Invasive Pulmonary Aspergillosis. Collectins, namely surfactant protein A (SP-A), surfactant protein D (SP-D) and mannan binding lectin (MBL), are pattern recognition molecules regulating both innate and adaptive immune response against pathogens. In the present review, we discussed various murine models of allergic and invasive aspergillosis and the role of collectins in host defense against aspergillosis.


Assuntos
Aspergilose/imunologia , Colectinas/fisiologia , Modelos Animais de Doenças , Animais , Camundongos
6.
J Immunol ; 191(12): 6117-27, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24174618

RESUMO

The complement system is an important part of the innate immune system. The complement cascade may be initiated downstream of the lectin activation pathway upon binding of mannan-binding lectin, ficolins, or collectin kidney 1 (CL-K1, alias CL-11) to suitable microbial patterns consisting of carbohydrates or acetylated molecules. During purification and characterization of native CL-K1 from plasma, we observed that collectin liver 1 (CL-L1) was copurified. Based on deglycosylation and nonreduced/reduced two-dimensional SDS-PAGE, we detected CL-K1 and CL-L1 in disulfide bridge-stabilized complexes. Heteromeric complex formation in plasma was further shown by ELISA and transient coexpression. Judging from the migration pattern on two-dimensional SDS-PAGE, the majority of plasma CL-K1 was found in complex with CL-L1. The ratio of this complex was in favor of CL-K1, suggesting that a heteromeric subunit is composed of one CL-L1 and two CL-K1 polypeptide chains. We found that the complex bound to mannan-binding lectin-associated serine proteases (MASPs) with affinities in the nM range in vitro and was associated with both MASP-1/-3 and MASP-2 in plasma. Upon binding to mannan or DNA in the presence of MASP-2, the CL-L1-CL-K1 complex mediated deposition of C4b. In favor of large oligomers, the activity of the complex was partly determined by the oligomeric size, which may be influenced by an alternatively spliced variant of CL-K1. The activity of the native heteromeric complexes was superior to that of recombinant CL-K1. We conclude that CL-K1 exists in circulation in the form of heteromeric complexes with CL-L1 that interact with MASPs and can mediate complement activation.


Assuntos
Colectinas/sangue , Complemento C4b/metabolismo , Lectina de Ligação a Manose da Via do Complemento , Serina Proteases Associadas a Proteína de Ligação a Manose/fisiologia , Processamento Alternativo , Sequência de Aminoácidos , Cromatografia de Afinidade , Colectinas/química , Colectinas/isolamento & purificação , Colectinas/fisiologia , DNA/imunologia , Humanos , Imunidade Inata , Mananas/imunologia , Dados de Sequência Molecular , Peso Molecular , Complexos Multiproteicos , Fragmentos de Peptídeos/química , Multimerização Proteica , Proteínas Recombinantes/metabolismo
7.
J Immunol ; 189(1): 112-9, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22615206

RESUMO

The lung environment actively inhibits apoptotic cell (AC) uptake by alveolar macrophages (AMøs) via lung collectin signaling through signal regulatory protein α (SIRPα). Even brief glucocorticoid (GC) treatment during maturation of human blood monocyte-derived or murine bone marrow-derived macrophages (Møs) increases their AC uptake. Whether GCs similarly impact differentiated tissue Møs and the mechanisms for this rapid response are unknown and important to define, given the widespread therapeutic use of inhaled GCs. We found that the GC fluticasone rapidly and dose-dependently increased AC uptake by murine AMøs without a requirement for protein synthesis. Fluticasone rapidly suppressed AMø expression of SIRPα mRNA and surface protein, and also activated a more delayed, translation-dependent upregulation of AC recognition receptors that was not required for the early increase in AC uptake. Consistent with a role for SIRPα suppression in rapid GC action, murine peritoneal Møs that had not been exposed to lung collectins showed delayed, but not rapid, increase in AC uptake. However, pretreatment of peritoneal Møs with the lung collectin surfactant protein D inhibited AC uptake, and fluticasone treatment rapidly reversed this inhibition. Thus, GCs act not only by upregulating AC recognition receptors during Mø maturation but also via a novel rapid downregulation of SIRPα expression by differentiated tissue Møs. Release of AMøs from inhibition of AC uptake by lung collectins may, in part, explain the beneficial role of inhaled GCs in inflammatory lung diseases, especially emphysema, in which there is both increased lung parenchymal cell apoptosis and defective AC uptake by AMøs.


Assuntos
Androstadienos/farmacologia , Proteínas Reguladoras de Apoptose/farmacologia , Apoptose/imunologia , Colectinas/fisiologia , Regulação para Baixo/imunologia , Tolerância Imunológica/imunologia , Macrófagos Alveolares/imunologia , Receptores Imunológicos/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/fisiologia , Células Cultivadas , Relação Dose-Resposta Imunológica , Regulação para Baixo/efeitos dos fármacos , Fluticasona , Tolerância Imunológica/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores Imunológicos/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
8.
Respir Physiol Neurobiol ; 173 Suppl: S43-54, 2010 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-20433956

RESUMO

This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins - the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfactant collectins capable of inhibiting foreign pathogens. Further aiding pulmonary host defence are non-surfactant collectins and antimicrobial peptides that are expressed across the biological kingdoms. Linking to the first symposium session, which emphasised molecular structure and biophysical function of surfactant lipids and proteins, this review begins with a discussion of the role of temperature and hydrostatic pressure in shaping the evolution of SP-C in mammals. Transitioning to the role of the alveolus in innate host defence we discuss the structure, function and regulation of antimicrobial peptides, the defensins and cathelicidins. We describe the recent discovery of novel avian collectins and provide evidence for their role in preventing influenza infection. This is followed by discussions of the roles of SP-A and SP-D in mediating host defence at the alveolar surface and in mediating inflammation and the allergic response of the airways. Finally we discuss the use of animal models of lung disease including knockouts to develop an understanding of the role of these proteins in initiating and/or perpetuating disease with the aim of developing new therapeutic strategies.


Assuntos
Colectinas/fisiologia , Evolução Molecular , Pneumopatias/metabolismo , Alvéolos Pulmonares/metabolismo , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/imunologia , Colectinas/imunologia , Humanos , Pressão Hidrostática , Pneumopatias/imunologia , Temperatura
9.
Sheng Wu Gong Cheng Xue Bao ; 26(1): 22-7, 2010 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-20353088

RESUMO

The grass carp (Ctenopharyngodon idella) collectin gene was cloned from mixed liver and kidney cDNA library. The full length sequence of grass carp collectin was 1128 bp, contained a 5' untranslated region of 229 bp and a 3' untranslated region of 104 bp. The open reading frame of grass carp collectin was 795 bp which could code a 264 amino acids polypeptide, including a terminal codon. Phylogenetic analyses showed that grass carp collectin shared the highest homology with that of zebrafish (Danio rerio). To understand the function of grass carp collectin, we expressed and purified the recombinant protein (P(CRD)) that comprised carbohydrate recognition domain (CRD). Agglutination of Aeromonas hydrophila and Staphylococcus aureus etc. and sugars inhibition experiments showed that: galactose, glucose, mannose and maltose could inhibit the agglutination of Aeromonas hydrophila. Maltose could lower the agglutination of Staphylococcus aureus, whereas peptidoglycan and glucose inhibited it well. In addition, the activity of grass carp collectin could not dependent on Ca(2+).


Assuntos
Carpas/genética , Colectinas/genética , Colectinas/fisiologia , Proteínas de Peixes/genética , Proteínas de Peixes/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Dados de Sequência Molecular , Filogenia , Peixe-Zebra/genética
10.
J Infect Dis ; 198(7): 1062-70, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18702607

RESUMO

BACKGROUND: Entamoeba histolytica, the cause of invasive amebiasis, phagocytoses apoptotic host cells during tissue invasion. In mammals, collectin family members (e.g., mannose-binding lectin [MBL]) and the structurally related protein C1q bind to apoptotic cells and stimulate macrophage phagocytosis via a conserved collagenous tail domain. The collectins also bind to bacteria, the usual source of nutrients for E. histolytica. METHODS: To test the possibility that the collectins are ligands that stimulate E. histolytica phagocytosis, we used a flow cytometry-based assay for amebic phagocytosis, a method for making single-ligand particles to delineate a given ligand's ability to initiate phagocytosis, and purified human C1q, MBL, and collagenous collectin tails. RESULTS: Apoptotic lymphocytes opsonized with serum or human C1q were phagocytosed more efficiently than control cells, an effect that was dependent on ligand density. C1q and the collectins alone were adequate to trigger amebic phagocytosis, because single-ligand particles coated with C1q, MBL, or purified collectin tails were phagocytosed more efficiently than control particles. Furthermore, C1q, MBL, and the tail domain of C1q were all chemoattractants for E. histolytica. CONCLUSIONS: C1q and MBL can serve as opsonins on apoptotic cells that stimulate E. histolytica phagocytosis, an effect mediated at least in part by the collagenous collectin tail domain.


Assuntos
Apoptose , Colectinas/fisiologia , Complemento C1q/fisiologia , Entamoeba histolytica/imunologia , Fagocitose , Animais , Linhagem Celular , Humanos , Lectina de Ligação a Manose/fisiologia
11.
Biochem Biophys Res Commun ; 363(1): 1-5, 2007 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-17825789

RESUMO

Collectrin is a type I membrane protein and shares significant homology with C-terminal domain of angiotensin-converting enzyme-2 (ACE2). However, collectrin lacks catalytic domain and it suggests the presence of uncharacterized physiological functions of collectrin. Collectrin is transcriptionally regulated by hepatocyte nuclear factor-alpha and -beta and is highly expressed on renal proximal tubules and collecting ducts as well as pancreatic beta-cells. Recent in vitro and in vivo studies demonstrated interesting physiological roles of collectrin related to insulin secretion, formation of primary cilia, renal cyst formation and amino acid transport. The common underlying molecular mechanism may be suggested by the evidence that collectrin binds to SNARE complex by interacting with snapin. Collectrin is involved in the process of vesicle transport and membrane fusion and thus it delivers insulin for exocytosis or various membrane proteins to apical plasmalemma and primary cilia. Collectrin may be the new therapeutic target for various pathological processes such as diabetes, polycystic kidney disease, hypertension and aminoaciduria.


Assuntos
Sistemas de Transporte de Aminoácidos/química , Sistemas de Transporte de Aminoácidos/fisiologia , Colectinas/química , Colectinas/fisiologia , Rim/metabolismo , Pâncreas/metabolismo , Transcrição Genética/fisiologia , Animais , Regulação da Expressão Gênica/fisiologia , Humanos , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/fisiologia
12.
J Neurosci Res ; 84(4): 874-90, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16868960

RESUMO

Accumulation of beta-amyloid protein (Abeta) in the brain is a hallmark of Alzheimer's disease (AD), and Abeta-mediated pathogenesis could result from increased production of Abeta or insufficient Abeta clearance by microglia, astrocytes, or the vascular system. Cell-surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of Abeta; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C-type lectin (SRCL), a member of the scavenger receptor family containing coiled-coil, collagen-like, and C-type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild-type mouse brain, in a double transgenic mouse model of AD (Tg-APP/PS1), immunohistochemistry showed that SRCL was markedly induced in Abeta-positive astrocytes and Abeta-positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg-APP/PS1 temporal cortex. The presence of a large number of SRCL/Abeta double-positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg-APP/PS1 mice and AD patients suggests a role for SRCL in Abeta clearance. Moreover, CHO-K1 cells transfected with SRCL isoforms were found to bind fibrillar Abeta(1-42). These findings suggest that SRCL could be the receptor involved in the binding or clearing of Abeta by glial and vascular/perivascular cells in AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Colectinas/fisiologia , Receptores Depuradores/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/farmacologia , Animais , Animais Recém-Nascidos , Anticoagulantes/farmacologia , Células Cultivadas , Córtex Cerebral/metabolismo , Cricetinae , Cricetulus , Interações Medicamentosas , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Polissacarídeos/farmacologia , Gravidez , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
13.
Curr Dir Autoimmun ; 9: 143-61, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16394659

RESUMO

The collagenous C-type lectin family (collectins) members are humoral molecules found in the serum and on certain mucosal surfaces. In humans the family of collectins include the mannose-binding lectin, surfactant protein A and surfactant protein D. They demonstrate broad ligand specificity for both pathogenic bacteria and viruses. Over the past 5 years data have emerged indicating that these molecules are able to bind self-derived ligands in the form of apoptotic cells and regulate inflammatory responses. Furthermore, exciting new data from murine models have begun to define the in vivo importance of these molecules as regulators of inflammation and immunity. Here will discuss our current understanding of the process of collectin recognition of dying and damaged cells and its implications for autoimmune and inflammatory diseases.


Assuntos
Apoptose , Colectinas/fisiologia , Inflamação/etiologia , Proteínas Opsonizantes/fisiologia , Animais , Antígenos CD/fisiologia , Autoimunidade , Ativação do Complemento , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Lectina de Ligação a Manose/fisiologia , Glicoproteínas de Membrana/fisiologia , Proteína A Associada a Surfactante Pulmonar/fisiologia , Proteína D Associada a Surfactante Pulmonar/fisiologia , Receptores de Complemento/fisiologia
14.
Pharmacol Ther ; 110(1): 14-34, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16226313

RESUMO

Inhalation of allergens in atopic patients results in a characteristic inflammatory response while in normal, healthy individuals it elicits no symptoms. The mechanisms by which the pulmonary immune system accomplishes elimination of inhaled particles and suppression of the ensuing inflammatory response are poorly understood. Based on their structural uniqueness, specific localization and functional versatility the hydrophilic surfactant proteins [surfactant protein (SP)-A and SP-D] are important candidate regulators of these processes. Recent studies in our laboratory and others indicated significant changes in levels of these molecules during the asthmatic response in animal models as well as in asthmatic patients. Because of their capability to directly inhibit T-cell activation and T-cell-dependent allergic inflammatory events, SP-A and SP-D may be significant contributors to the local control of T-helper (Th)2-type inflammation in the airways. This review will discuss their relevant structural-functional features and recent evidence supporting the hypothesis that SP-A and SP-D have a role in regulation of allergic airway sensitization.


Assuntos
Colectinas/fisiologia , Pulmão/fisiologia , Hipersensibilidade Respiratória/imunologia , Humanos , Proteína A Associada a Surfactante Pulmonar/imunologia , Proteína D Associada a Surfactante Pulmonar/imunologia
15.
Blood ; 107(1): 143-50, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16166590

RESUMO

Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The alpha2beta1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that alpha2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Peritoneal mast cells require alpha2beta1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the alpha2beta1 integrin induces activation and cytokine secretion remain unknown. We now report that the alpha2beta1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the alpha2beta1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the alpha2beta1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.


Assuntos
Imunidade Inata , Mastócitos/metabolismo , Glicoproteínas de Membrana/fisiologia , Receptores de Complemento/fisiologia , Animais , Complexo Antígeno-Anticorpo/farmacologia , Colectinas/fisiologia , Citocinas/metabolismo , Integrina alfa2beta1/fisiologia , Interleucina-6/metabolismo , Ligantes , Camundongos , Camundongos Knockout , Peritônio/citologia , Ligação Proteica
16.
J Endotoxin Res ; 11(3): 181-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15949147

RESUMO

After penetration into the lower airways, bacterial lipopolysaccharide (LPS) interacts with alveolar cells in a fluid environment consisting of pulmonary surfactant, a lipid-protein complex which prevents alveolar collapsing and participates in lung defense. The two hydrophilic surfactant components SP-A and SP-D are proteins with collagen-like and lectin domains (collectins) able to interact with carbohydrate-containing ligands present on microbial membranes, and with defined regions of LPS. This explains their capacity to damage the bacterial envelope and induce an antimicrobial effect. In addition, they modulate LPS-induced production of pro-inflammatory mediators in leukocytes by interaction with LPS or with leukocyte receptors. A third surfactant component, SP-C, is a small, highly hydrophobic lipopeptide which interacts with lipid A and reduces LPS-induced effects in macrophages and splenocyte cultures. The interaction of the different SPs with CD14 might explain their ability to modulate some LPS responses. Although the alveolar fluid contains other antiLPS and antimicrobial agents, SPs are the most abundant proteins which might contribute to protect the lung epithelium and reduce the incidence of LPS-induced lung injury. The presence of the surfactant collectins SP-A and SP-D in non-pulmonary tissues, such as the female genital tract, extends their field of action to other mucosal surfaces.


Assuntos
Lipopolissacarídeos , Pulmão/imunologia , Pulmão/microbiologia , Surfactantes Pulmonares/farmacologia , Sequência de Aminoácidos , Colectinas/fisiologia , Humanos , Inflamação , Receptores de Lipopolissacarídeos , Dados de Sequência Molecular , Alvéolos Pulmonares
18.
Cell Mol Biol (Noisy-le-grand) ; 50 Online Pub: OL639-48, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15579257

RESUMO

This article reviews recent findings regarding interrelationships between the pulmonary surfactant system and alveolar macrophages in the pathogenesis of human lung diseases, including pulmonary alveolar proteinosis, pulmonary infection, inflammation and obstructive lung diseases. Various components of pulmonary surfactant interact with alveolar macrophages in the modulation of innate host defense responses of the lung. In a reciprocal manner, alveolar macrophages regulate surfactant homeostasis, influencing rates of surfactant protein and phospholipid clearance and catabolism. Increasing evidence suggests that the complex interactions between the surfactant system and the alveolar macrophage are intrinsically linked to development of various lung diseases.


Assuntos
Pneumopatias/etiologia , Macrófagos Alveolares/fisiologia , Surfactantes Pulmonares/metabolismo , Animais , Diferenciação Celular/fisiologia , Colectinas/fisiologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Humanos , Pneumopatias/genética , Pneumopatias/imunologia , Transdução de Sinais , Transcrição Genética
19.
J Immunol ; 172(12): 7592-602, 2004 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15187139

RESUMO

Collectins, including surfactant proteins A (SP-A) and D (SP-D) and mannose binding lectin (MBL), are the important constituents of the innate immune system. Mycobacterium avium, a facultative intracellular pathogen, has developed numerous mechanisms for entering mononuclear phagocytes. In this study, we investigated the interactions of collectins with M. avium and the effects of these lectins on phagocytosis of M. avium by macrophages. SP-A, SP-D, and MBL exhibited a concentration-dependent binding to M. avium. The binding of SP-A to M. avium was Ca(2+)-dependent but that of SP-D and MBL was Ca(2+)-independent. SP-A and SP-D but not MBL enhanced the phagocytosis of FITC-labeled M. avium by rat alveolar macrophages and human monocyte-derived macrophages. Excess mannan, zymosan, and lipoarabinomannan derived from the M. avium-intracellular complex, significantly decreased the collectin-stimulated phagocytosis of M. avium. Enhanced phagocytosis was not affected by the presence of cycloheximide or chelation of Ca(2+). The mutated collectin, SP-A(E195Q, R197D) exhibited decreased binding to M. avium but stimulated phagocytosis to a level comparable to wild-type SP-A. Enhanced phagocytosis by cells persisted even after preincubation and removal of SP-A or SP-D. Rat alveolar macrophages that had been incubated with SP-A or SP-D also exhibited enhanced uptake of (125)I-mannosylated BSA. Analysis by confocal microscopy and flow cytometry revealed that the lung collectins up-regulated the cell surface expression of mannose receptor on monocyte-derived macrophages. These results provide compelling evidence that SP-A and SP-D enhance mannose receptor-mediated phagocytosis of M. avium by macrophages.


Assuntos
Colectinas/fisiologia , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Mycobacterium avium/imunologia , Fagocitose/imunologia , Receptores de Superfície Celular/metabolismo , Animais , Colectinas/metabolismo , Humanos , Pulmão/química , Macrófagos/imunologia , Macrófagos Alveolares/imunologia , Lectina de Ligação a Manose/metabolismo , Lectina de Ligação a Manose/fisiologia , Monócitos/imunologia , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína A Associada a Surfactante Pulmonar/fisiologia , Proteína D Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/fisiologia , Ratos , Ratos Sprague-Dawley , Regulação para Cima
20.
Eur J Biochem ; 271(7): 1229-49, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15030473

RESUMO

Collectins are a family of collagenous calcium-dependent defense lectins in animals. Their polypeptide chains consist of four regions: a cysteine-rich N-terminal domain, a collagen-like region, an alpha-helical coiled-coil neck domain and a C-terminal lectin or carbohydrate-recognition domain. These polypeptide chains form trimers that may assemble into larger oligomers. The best studied family members are the mannan-binding lectin, which is secreted into the blood by the liver, and the surfactant proteins A and D, which are secreted into the pulmonary alveolar and airway lining fluid. The collectins represent an important group of pattern recognition molecules, which bind to oligosaccharide structures and/or lipid moities on the surface of microorganisms. They bind preferentially to monosaccharide units of the mannose type, which present two vicinal hydroxyl groups in an equatorial position. High-affinity interactions between collectins and microorganisms depend, on the one hand, on the high density of the carbohydrate ligands on the microbial surface, and on the other, on the degree of oligomerization of the collectin. Apart from binding to microorganisms, the collectins can interact with receptors on host cells. Binding of collectins to microorganisms may facilitate microbial clearance through aggregation, complement activation, opsonization and activation of phagocytosis, and inhibition of microbial growth. In addition, the collectins can modulate inflammatory and allergic responses, affect apoptotic cell clearance and modulate the adaptive immune system.


Assuntos
Colectinas/química , Colectinas/fisiologia , Sistema Imunitário/fisiologia , Animais , Proteínas de Bactérias/química , Carboidratos/química , Epitopos/química , Proteínas Fúngicas/química , Humanos , Inflamação , Lipídeos/química , Modelos Biológicos , Monossacarídeos/química , Polissacarídeos/química , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Virais/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...