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Mucosal Immunol ; 7(2): 292-303, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23820751

RESUMO

Eosinophil accumulation in health and disease is a hallmark characteristic of mucosal immunity and type 2 helper T cell (Th2) inflammation. Eotaxin-induced CCR3 (chemokine (C-C motif) receptor 3) signaling has a critical role in eosinophil chemotactic responses. Nevertheless, the expressions of immunoreceptor tyrosine-based inhibitory motif-bearing receptors such as CMRF35-like molecule-1 (CLM-1) and their ability to govern eosinophil migration are largely unknown. We now report that CLM-1 (but not CLM-8) is highly and distinctly expressed by colonic and adipose tissue eosinophils. Furthermore, Clm1⁻/⁻ mice display elevated baseline tissue eosinophilia. CLM-1 negatively regulated eotaxin-induced eosinophil responses including eosinophil chemotaxis, actin polymerization, calcium influx, and extracellular signal-regulated kinase (ERK)-1/2, but not p38 phosphorylation. Addition of CLM-1 ligand (e.g., phosphatidylserine) rendered wild-type eosinophils hypochemotactic in vitro and blockade of CLM-1/ligand interactions rendered wild-type eosinophils hyperchemotactic in vitro and in vivo in a model of allergic airway disease. Interestingly, suppression of cellular recruitment via CLM-1 was specific to eosinophils and eotaxin, as leukotriene B4 (LTB4)- and macrophage inflammatory protein-1α (MIP-1α)-induced eosinophil and neutrophil migration were not negatively regulated by CLM-1. Finally, peripheral blood eosinophils obtained from allergic rhinitis patients displayed elevated CLM-1/CD300f levels. These data highlight CLM-1 as a novel regulator of eosinophil homeostasis and demonstrate that eosinophil accumulation is constantly governed by CLM-1, which negatively regulates eotaxin-induced eosinophil responses.


Assuntos
Quimiotaxia/fisiologia , Eosinófilos/imunologia , Eosinófilos/metabolismo , Homeostase , Receptores Imunológicos/metabolismo , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Quimiocina CCL11/farmacologia , Quimiocina CCL24/farmacologia , Quimiocina CCL3/farmacologia , Quimiotaxia/efeitos dos fármacos , Colo/imunologia , Colo/metabolismo , Eosinófilos/efeitos dos fármacos , Humanos , Leucotrieno B4/farmacologia , Ligantes , Camundongos , Camundongos Knockout , Ligação Proteica , Receptores Imunológicos/genética , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/metabolismo
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