TY - JOUR
T1 - Novel collectin/C1q receptor mediates mast cell activation and innate immunity
AU - Edelson, Brian T.
AU - Stricker, Thomas P.
AU - Li, Zhengzhi
AU - Dickeson, S. Kent
AU - Shepherd, Virginia L.
AU - Santoro, Samuel A.
AU - Zutter, Mary M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/1/1
Y1 - 2006/1/1
N2 - 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 α2β1 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 α2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes - and zymosan-induced peritonitis. Peritoneal mast cells require α2β1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the α2β1 integrin induces activation and cytokine secretion remain unknown. We now report that the α2β1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the α2β1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the α2β1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.
AB - 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 α2β1 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 α2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes - and zymosan-induced peritonitis. Peritoneal mast cells require α2β1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the α2β1 integrin induces activation and cytokine secretion remain unknown. We now report that the α2β1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the α2β1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the α2β1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.
UR - http://www.scopus.com/inward/record.url?scp=30144437677&partnerID=8YFLogxK
U2 - 10.1182/blood-2005-06-2218
DO - 10.1182/blood-2005-06-2218
M3 - Article
C2 - 16166590
AN - SCOPUS:30144437677
VL - 107
SP - 143
EP - 150
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -