Novel collectin/C1q receptor mediates mast cell activation and innate immunity.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Edelson BT,Stricker TP,Li Z,Dickeson SK,Shepherd VL,Santoro SA,Zutter MM

doi

10.1182/blood-2005-06-2218

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

143-50

issue

1

eissn

0006-4971

issn

1528-0020

pii

2005-06-2218

journal_volume

107

pub_type

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