DECREASED RESISTANCE TO BACTERIAL-INFECTION AND GRANULOCYTE DEFECTS IN IAP-DEFICIENT MICE

Granulocyte [polymorphonuclear leucocyte (PMN)] migration to sites of infection and subsequent activation is essential for host defense. Gen e-targeted mice deficient for integrin-associated protein (IAP, also t ermed CD47) succumbed to Escherichia coli peritonitis at inoccula surv ived by heterozygous littermates. In vivo, they had an early defect in PMN accumulation at the site of infection. In vitro, IAP(-/-) PMNs we re deficient in beta(3) integrin-dependent ligand binding, activation oi an oxidative burst, and Fc receptor-mediated phagocytosis. Thus, IA P plays a key role in host defense by participating both in PMN migrat ion in response to bacterial infection and in PMN activation at extrav ascular sites.