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Blood, 1 August 2004, Vol. 104, No. 3, pp. 832-839. Prepublished online as a Blood First Edition Paper on April 8, 2004; DOI 10.1182/blood-2003-07-2624. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2624v1 104/3/832    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Abdel-Latif, D. Articles by Lacy, P. Search for Related Content PubMed PubMed Citation Articles by Abdel-Latif, D. Articles by Lacy, P. Related Collections Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Rac2 is critical for neutrophil primary granule exocytosis Dalia Abdel-Latif, Melissa Steward, Dawn L. Macdonald, Gordon A. Francis, Mary C. Dinauer, and Paige Lacy From the Pulmonary Research Group and the Canadian Institutes of Health Research (CIHR) Group on Molecular and Cell Biology of Lipids, Department of Medicine, University of Alberta, Edmonton, AB, Canada, and the Department of Pediatrics (Hematology/Oncology) and Medical and Molecular Genetics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis. Neutrophil degranulation is important in many inflammatory disorders, although the intracellular mechanisms underlying this process remain poorly understood. The Rho GTPase, Rac2, has been implicated in control of degranulation in earlier studies. We hypothesized that Rac2 selectively regulates neutrophil primary granule release. Using bone marrow and peritoneal exudate neutrophils from rac2-/- mice in comparison with similar cells from wild-type C57Bl/6 mice, we found that primary granule myeloperoxidase and elastase release was absent in Rac2-/- neutrophils in response to chemoattractant stimulation, cytochalasin B/f-Met-Leu-Phe (CB/fMLP), and CB/leukotriene B4. Rac2-/- neutrophils also failed to exhibit mobilization of the primary granule marker CD63+ during CB/fMLP stimulation as determined by confocal microscopy. Priming of Rac2-/- neutrophils with tumor necrosis factor (TNF) or by peritoneal elicitation did not rescue the defect in primary granule release. However, phosphorylation of p38 mitogen-activated protein (MAP) kinase in Rac2-/- neutrophils was evident in response to CB/fMLP and/or TNF. Primary granule density and morphology were normal in Rac2-/- neutrophils. Secondary specific and tertiary granule release, measured by lactoferrin immunoassay and zymography, was normal in response to CB/fMLP and adhesion to fibronectin. These findings suggest an obligatory role for Rac2 in regulation of primary granule release by neutrophils. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Cunnick, S. Schmidhuber, G. Chen, M. Yu, S.-J. Yi, Y. J. Cho, V. Kaartinen, P. Minoo, D. Warburton, J. Groffen, et al. Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses Mol. Cell. Biol., November 1, 2009; 29(21): 5742 - 5750. [Abstract] [Full Text] [PDF] A. Daryadel, S. Yousefi, D. Troi, I. Schmid, J. Schmidt-Mende, C. Mordasini, C. A. Dahinden, A. Ziemiecki, and H.-U. Simon RhoH/TTF Negatively Regulates Leukotriene Production in Neutrophils J. Immunol., May 15, 2009; 182(10): 6527 - 6532. [Abstract] [Full Text] [PDF] F. Momboisse, E. Lonchamp, V. Calco, M. Ceridono, N. Vitale, M.-F. Bader, and S. Gasman {beta}PIX-activated Rac1 stimulates the activation of phospholipase D, which is associated with exocytosis in neuroendocrine cells J. Cell Sci., March 15, 2009; 122(6): 798 - 806. [Abstract] [Full Text] [PDF] T. Mitchell, A. Lo, M. R. Logan, P. Lacy, and G. Eitzen Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1354 - C1365. [Abstract] [Full Text] [PDF] P. P. Ward, M. Mendoza-Meneses, P. W. Park, and O. M. Conneely Stimulus-Dependent Impairment of the Neutrophil Oxidative Burst Response in Lactoferrin-Deficient Mice Am. J. Pathol., April 1, 2008; 172(4): 1019 - 1029. [Abstract] [Full Text] [PDF] J. Wang, H. Jiao, T. L. Stewart, M. V. H. Lyons, H. A. Shankowsky, P. G. Scott, and E. E. Tredget Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes J. 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Saito Isoform-Specific Membrane Targeting Mechanism of Rac during Fc{gamma}R-Mediated Phagocytosis: Positive Charge-Dependent and Independent Targeting Mechanism of Rac to the Phagosome J. Immunol., August 15, 2005; 175(4): 2381 - 2390. [Abstract] [Full Text] [PDF] S. Corbetta, S. Gualdoni, C. Albertinazzi, S. Paris, L. Croci, G. G. Consalez, and I. de Curtis Generation and Characterization of Rac3 Knockout Mice Mol. Cell. Biol., July 1, 2005; 25(13): 5763 - 5776. [Abstract] [Full Text] [PDF] S. Chakrabarti and K. D. Patel Regulation of matrix metalloproteinase-9 release from IL-8-stimulated human neutrophils J. Leukoc. Biol., July 1, 2005; 78(1): 279 - 288. [Abstract] [Full Text] [PDF] 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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