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

Research output: Contribution to journalArticle

444 Citations (Scopus)

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

Fingerprint

rho GTP-Binding Proteins
Neutrophils
Exudates and Transudates
rac GTP-Binding Proteins
L-Selectin
Aspergillus fumigatus
Mitogen-Activated Protein Kinase 1
Chemotactic Factors
Chemotaxis
Superoxides
Actins
Mammals
Bone Marrow
Mortality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Roberts, A. W., Chaekyun, K., Zhen, L., Lowe, J. B., Kapur, R., Petryniak, B., ... 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.

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. / Roberts, Andrew W.; Chaekyun, Kim; Zhen, Ling; Lowe, John B.; Kapur, Reuben; Petryniak, Bronislawa; Spaetti, Adam; Pollock, Jonathan D.; Borneo, Jovencio B.; Bradford, Gillian B.; Atkinson, Simon J.; Dinauer, Mary C.; Williams, David A.

In: Immunity, Vol. 10, No. 2, 02.1999, p. 183-196.

Research output: Contribution to journalArticle

Roberts, AW, Chaekyun, K, Zhen, L, Lowe, JB, Kapur, R, Petryniak, B, Spaetti, A, Pollock, JD, Borneo, JB, Bradford, GB, Atkinson, SJ, Dinauer, MC & Williams, DA 1999, 'Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense', Immunity, vol. 10, no. 2, pp. 183-196.
Roberts, Andrew W. ; Chaekyun, Kim ; Zhen, Ling ; Lowe, John B. ; Kapur, Reuben ; Petryniak, Bronislawa ; Spaetti, Adam ; Pollock, Jonathan D. ; Borneo, Jovencio B. ; Bradford, Gillian B. ; Atkinson, Simon J. ; Dinauer, Mary C. ; Williams, David A. / Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. In: Immunity. 1999 ; Vol. 10, No. 2. pp. 183-196.
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