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

Andrew W. Roberts, Kim Chaekyun, Ling Zhen, John B. Lowe, Reuben Kapur, Bronislawa Petryniak, Adam Spaetti, Jonathan D. Pollock, Jovencio B. Borneo, Gillian B. Bradford, Simon J. Atkinson, Mary C. Dinauer, David A. Williams

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454 Scopus citations

Abstract

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2(-/-) neutrophils displayed significant 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 chemoattractants. Superoxide production by rac2(-/-) bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.

Original languageEnglish (US)
Pages (from-to)183-196
Number of pages14
JournalImmunity
Volume10
Issue number2
DOIs
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Roberts, A. W., Chaekyun, K., Zhen, L., Lowe, J. B., Kapur, R., Petryniak, B., Spaetti, A., Pollock, J. D., Borneo, J. B., Bradford, G. B., Atkinson, S. J., Dinauer, M. C., & Williams, D. A. (1999). Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity, 10(2), 183-196. https://doi.org/10.1016/S1074-7613(00)80019-9