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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2214-2220.
Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-08-2978.


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IMMUNOBIOLOGY

Mast cell–mediated inflammatory responses require the {alpha}2{beta}1 integrin

Brian T. Edelson, Zhengzhi Li, Loretta K. Pappan, and Mary M. Zutter

From the Departments of Pathology and Immunology and Cell Biology, Washington University School of Medicine, St Louis, MO; and the Departments of Pathology and Cancer Biology, Vanderbilt University School of Medicine, The Vanderbilt Clinic, Nashville, TN.

Although the {alpha}2{beta}1 integrin is widely expressed and has been extensively studied, it has not been previously implicated in mast cell biology. We observed that {alpha}2 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 {alpha}2{beta}1 integrin, it seemed unlikely that this integrin mediated neutrophil migration directly. Here, we demonstrate constitutive {alpha}2{beta}1 integrin expression on peritoneal mast cells. Although {alpha}2-null mice contain normal numbers of peritoneal mast cells, these {alpha}2-null cells do not support in vivo mast cell–dependent inflammatory responses. We conclude that {alpha}2{beta}1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection.


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