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* Brigham and Women’s Hospital, Boston, MA 02115;
University of Toronto, Toronto, Canada;
Department of Pediatrics (Hematology/Oncology), Indiana University School of Medicine, Indianapolis, IN 46202;
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
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Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany; and
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Department of Medicine, Division of Respirology, and The Toronto General Hospital Research Institute of the University Health Network, Toronto, Canada
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.
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Z. T. Kneass and R. B. Marchase Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils J. Biol. Chem., April 15, 2005; 280(15): 14579 - 14585. [Abstract] [Full Text] [PDF]
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A. Yamauchi, C. C. Marchal, J. Molitoris, N. Pech, U. Knaus, J. Towe, S. J. Atkinson, and M. C. Dinauer Rac GTPase Isoform-specific Regulation of NADPH Oxidase and Chemotaxis in Murine Neutrophils in Vivo: ROLE OF THE C-TERMINAL POLYBASIC DOMAIN J. Biol. Chem., January 14, 2005; 280(2): 953 - 964. [Abstract] [Full Text] [PDF]
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R. He, M. Nanamori, H. Sang, H. Yin, M. C. Dinauer, and R. D. Ye Reconstitution of Chemotactic Peptide-Induced Nicotinamide Adenine Dinucleotide Phosphate (Reduced) Oxidase Activation in Transgenic COS-phox Cells J. Immunol., December 15, 2004; 173(12): 7462 - 7470. [Abstract] [Full Text] [PDF]
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C. X. Sun, G. P. Downey, F. Zhu, A. L. Y. Koh, H. Thang, and M. Glogauer Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass Blood, December 1, 2004; 104(12): 3758 - 3765. [Abstract] [Full Text] [PDF]
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A. Yamauchi, C. Kim, S. Li, C. C. Marchal, J. Towe, S. J. Atkinson, and M. C. Dinauer Rac2-Deficient Murine Macrophages Have Selective Defects in Superoxide Production and Phagocytosis of Opsonized Particles J. Immunol., November 15, 2004; 173(10): 5971 - 5979. [Abstract] [Full Text] [PDF]
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R. Nijhara, P. B. van Hennik, M. L Gignac, M. J. Kruhlak, P. L. Hordijk, J. Delon, and S. Shaw Rac1 Mediates Collapse of Microvilli on Chemokine-Activated T Lymphocytes J. Immunol., October 15, 2004; 173(8): 4985 - 4993. [Abstract] [Full Text] [PDF]
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M. T. Quinn and K. A. Gauss Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases J. Leukoc. Biol., October 1, 2004; 76(4): 760 - 781. [Abstract] [Full Text] [PDF]
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M. A. M. Gakidis, X. Cullere, T. Olson, J. L. Wilsbacher, B. Zhang, S. L. Moores, K. Ley, W. Swat, T. Mayadas, and J. S. Brugge Vav GEFs are required for {beta}2 integrin-dependent functions of neutrophils J. Cell Biol., July 19, 2004; 166(2): 273 - 282. [Abstract] [Full Text] [PDF]
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Y. Gu, M.-D. Filippi, J. A. Cancelas, J. E. Siefring, E. P. Williams, A. C. Jasti, C. E. Harris, A. W. Lee, R. Prabhakar, S. J. Atkinson, et al. Hematopoietic Cell Regulation by Rac1 and Rac2 Guanosine Triphosphatases Science, October 17, 2003; 302(5644): 445 - 449. [Abstract] [Full Text] [PDF]
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