Document Detail

Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles.
MedLine Citation:
PMID:  15528331     Owner:  NLM     Status:  MEDLINE    
The Rho family GTPase Rac is a crucial participant in numerous cellular functions and acts as a molecular switch for signal transduction. Mice deficient in hemopoietic-specific Rac2 exhibited agonist-specific defects in neutrophil functions including chemoattractant-stimulated filamentous actin polymerization and chemotaxis, and superoxide production elicited by phorbol ester, fMLP, or IgG-coated particles, despite expression of the highly homologous Rac1 isoform. In this study, functional responses of Rac2-null murine macrophages were characterized to examine whether Rac2 also has nonredundant functions in this phagocytic lineage. In contrast to murine neutrophils, in which Rac1 and Rac2 are present in similar amounts, Rac1 was approximately 4-fold more abundant than Rac2 in both bone marrow-derived and peritoneal exudate macrophages, and macrophage Rac1 levels were unchanged by the absence of Rac2. Accumulation of exudate macrophages during peritoneal inflammation was reduced in rac2(-/-) mice. FcgammaR-mediated phagocytosis of IgG-coated SRBC was also significantly decreased in Rac2-null macrophages, as was NADPH oxidase activity in response to phorbol ester or FcgammaR stimulation. However, phagocytosis and oxidant production stimulated by serum-opsonized zymosan was normal in rac2(-/-) macrophages. Macrophage morphology was also similar in wild-type and Rac2-null cells, as was actin polymerization induced by FcgammaR-mediated phagocytosis or M-CSF. Hence, Rac2-null macrophages have selective defects paralleling many of the observed functional defects in Rac2-null neutrophils. These results provide genetic evidence that although Rac2 is a relatively minor isoform in murine macrophages, it plays a nonoverlapping role with Rac1 to regulate host defense functions in this phagocyte lineage.
Akira Yamauchi; Chaekyun Kim; Shijun Li; Christophe C Marchal; Jason Towe; Simon J Atkinson; Mary C Dinauer
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  173     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-05     Completed Date:  2004-12-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5971-9     Citation Subset:  AIM; IM    
Inha University College of Medicine, Incheon, Korea.
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MeSH Terms
Actins / metabolism
Antigens, Surface / biosynthesis
Ascitic Fluid / cytology,  immunology
Bone Marrow Cells / enzymology,  immunology,  metabolism
Cell Migration Inhibition
Cells, Cultured
Erythrocytes / immunology
Immunoglobulin G / blood,  metabolism
Macrophage Colony-Stimulating Factor / pharmacology
Macrophages / enzymology,  immunology*,  metabolism*
Macrophages, Peritoneal / enzymology,  immunology,  metabolism
Mice, Inbred C57BL
Mice, Knockout
Opsonin Proteins / blood,  metabolism*
Oxidants / biosynthesis
Phagocytosis / genetics*,  immunology
Phorbol Esters / pharmacology
Protein Isoforms / biosynthesis,  deficiency,  genetics
Receptors, IgG / physiology
Superoxides / metabolism*
rac GTP-Binding Proteins / biosynthesis,  deficiency*,  genetics*
rac1 GTP-Binding Protein / biosynthesis,  physiology
Grant Support
Reg. No./Substance:
0/Actins; 0/Antigens, Surface; 0/Immunoglobulin G; 0/Opsonin Proteins; 0/Oxidants; 0/Phorbol Esters; 0/Protein Isoforms; 0/Receptors, IgG; 11062-77-4/Superoxides; 81627-83-0/Macrophage Colony-Stimulating Factor; EC 3.6.1.-/rac2 GTP-binding protein; EC GTP-Binding Proteins; EC GTP-Binding Protein

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