Rac2-Deficient Murine Macrophages Have Selective Defects in Superoxide Production and Phagocytosis of Opsonized Particles

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 poly...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-11, Vol.173 (10), p.5971-5979
Main Authors: Yamauchi, Akira, Kim, Chaekyun, Li, Shijun, Marchal, Christophe C, Towe, Jason, Atkinson, Simon J, Dinauer, Mary C
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Antigens, Surface - biosynthesis
Ascitic Fluid - cytology
Ascitic Fluid - immunology
Bone Marrow Cells - enzymology
Bone Marrow Cells - immunology
Bone Marrow Cells - metabolism
Cell Migration Inhibition
Cells, Cultured
Erythrocytes - immunology
Female
Immunoglobulin G - blood
Immunoglobulin G - metabolism
Macrophage Colony-Stimulating Factor - pharmacology
Macrophages - enzymology
Macrophages - immunology
Macrophages - metabolism
Macrophages, Peritoneal - enzymology
Macrophages, Peritoneal - immunology
Macrophages, Peritoneal - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Opsonin Proteins - blood
Opsonin Proteins - metabolism
Oxidants - biosynthesis
Phagocytosis - genetics
Phagocytosis - immunology
Phorbol Esters - pharmacology
Protein Isoforms - biosynthesis
Protein Isoforms - deficiency
Protein Isoforms - genetics
rac GTP-Binding Proteins - biosynthesis
rac GTP-Binding Proteins - deficiency
rac GTP-Binding Proteins - genetics
rac1 GTP-Binding Protein - biosynthesis
rac1 GTP-Binding Protein - physiology
RAC2 GTP-Binding Protein
Receptors, IgG - physiology
Sheep
Superoxides - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.10.5971