Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense

In mammals, the Rho family GTPase Rac2 is restricted in expression to hemat opoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Pac proteins in hematopoietic cells, rac2(-/-) neutrophils displayed significa nt defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/ p44 MAP kinase activation induced by chemoattracta nts. Superoxide production by rac2(-/-) bone marrow neutrophils was signifi cantly reduced compared to wild type, but it was normal in activated perito neal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increa sed mortality when challenged with Aspergillus fumigatus. Rac2 is an essent ial regulator of multiple specialized neutrophil functions.