Mast cell-mediated inflammatory responses require the α2β1 integrin

Although the alpha2beta1 integrin is widely expressed and has been extensively studied, it has not been previously implicated in mast cell biology. We observed that alpha2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and interleukin-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Since exudative neutrophils of wild-type mice expressed little alpha2beta1 integrin, it seemed unlikely that this integrin mediated neutrophil migration directly. Here, we demonstrate constitutive alpha2beta1 integrin expression on peritoneal mast cells. Although alpha2-null mice contain normal numbers of peritoneal mast cells, these alpha2-null cells do not support in vivo mast cell-dependent inflammatory responses. We conclude that alpha2beta1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection. (C) 2004 by The American Society of Hematology.