Mast cell-mediated inflammatory responses require the alpha 2 beta 1 integrin.
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.
Edelson
Brian T
BT
Department of Pathology, Washington University School of Medicine, St Louis, MO, USA.
Li
Zhengzhi
Z
Pappan
Loretta K
LK
Zutter
Mary M
MM
D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D004195:Disease Models, Animal; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010529:Peritoneal Cavity / Q000166:cytology
D039421:Integrin alpha2; D038982:Integrin alpha2beta1