Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions.
Defects in myeloid cell function in Rac2 knockout mice underline the importance of this isoform in activation of NADPH oxidase and cell motility. However, the specific role of Rac1 in neutrophil function has been difficult to assess since deletion of Rac1 results in embryonic lethality in mice. To elucidate the specific role of Rac1 in neutrophils, we generated mice with a conditional Rac1 deficiency restricted to cells of the granulocyte/monocyte lineage. As observed in Rac2-deficient neutrophils, Rac1-deficient neutrophils demonstrated profound defects in inflammatory recruitment in vivo, migration to chemotactic stimuli, and chemoattractant-mediated actin assembly. In contrast, superoxide production is normal in Rac1-deficient neutrophils but markedly diminished in Rac2 null cells. These data demonstrate that although Rac1 and Rac2 are both required for actin-mediated functions, Rac2 is specifically required for activation of the neutrophil NADPH oxidase.
Glogauer
Michael
M
Brigham and Women's Hospital, Boston, MA 02115, USA. michael.glogauer@utoronto.ca
Marchal
Christophe C
CC
Zhu
Fei
F
Worku
Aelaf
A
Clausen
Björn E
BE
Foerster
Irmgard
I
Marks
Peter
P
Downey
Gregory P
GP
Dinauer
Mary
M
Kwiatkowski
David J
DJ
D000199:Actins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D000818:Animals; D001202:Ascitic Fluid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003433:Crosses, Genetic; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D000097766:RAC2 GTP-Binding Protein
D000199:Actins; D013481:Superoxides; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein