Novel collectin/C1q receptor mediates mast cell activation and innate immunity
Novel collectin/C1q receptor mediates mast cell activation and innate immunity
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DOI：
10.1182/blood-2005-06-2218
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发表时间：
2006-01-01
期刊：
影响因子：
20.3
通讯作者：
Zutter, MM
中科院分区：
文献类型：
--
作者：
Edelson, BT;Stricker, TP;Zutter, MM
肥大细胞在先天免疫、过敏和自身免疫性疾病中起关键作用。介导肥大细胞激活的受体/配体的相互作用还没有明确的定义。α(2)β(1)整合素是胶原蛋白、层粘连蛋白、核心蛋白、E-钙粘附素、基质金属蛋白酶-1(MMP1)、内皮膜蛋白和几种病毒的受体，参与正常的发育、炎症和肿瘤形成过程。我们最近报道，在单核细胞增多性李斯特菌和酵母多糖诱导的腹膜炎中，整合素亚单位缺失的α(2)小鼠表现出明显的中性粒细胞和IL-6反应减弱。腹膜肥大细胞需要α(2)β(1)整合素的表达来激活对病原体的反应，但α(2)β(1)整合素诱导激活和细胞因子分泌的配体和分子机制尚不清楚。我们现在报道，α(2)β(1)整合素是一种新的多种集合素和C1q补体蛋白的受体。我们证明，α(2)β(1)整合素提供肥大细胞激活和细胞因子分泌所需的共刺激功能。这一发现表明，α(2)β(1)整合素不仅对先天免疫很重要，而且可能是调节自身免疫/变态反应性疾病的关键靶点。
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 alpha(2)beta(1) 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 alpha(2) integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Peritoneal mast cells require alpha(2)beta(1) integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the alpha(2)beta(1) integrin induces activation and cytokine secretion remain unknown. We now report that the alpha(2)beta(1) integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the alpha(2)beta(1) integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the alpha(2)beta(1) integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.