Rac2-deficient neutrophils have selective defects in superoxide production, F-actin polymerization and phagocytosis

초록

Rac2 is a hematopoietic-specific Rho-GTPase implicated as an important constituent of the NADPH oxidase complex. We previously reported that PMA-induced superoxide production was reduced in Rac2-null neutrophils and partially corrected in TNF-a primed neutrophils. We further investigated the regulatory role of Rac2 in murine neutrophils. Superoxide production was reduced in Rac2-null neutrophils in response to PMA, fMLP and IgG-coated sheep red blood cells, whereas normal in response to serum-opsonized zymosan (SOZ). Interestingly, arachidonic acid (AA) fully restored PMA-elicited superoxide production, whereas AA alone did not rescue NADPH oxidase activity in Rac2-null neutrophils. In addition, AA has no effect on fMLP-elicited superoxide production. Filamentous actin polymerization in response to fMLP, IL-8, LTB4, PMA or AA was also reduced in Rac2-null neutrophils, but was not restored by co-stimulation with PMA and AA. Phagocytosis of SOZ was normal in Rac2-null neutrophils, while FcgR-mediated phagocytosis was impaired. Taken together, these observations suggest that there are agonist- and pathway-specific differences in the underlying basis of functional defects in Rac2-null neutrophils.