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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5193-5201. Prepublished online as a Blood First Edition Paper on September 29, 2008; DOI 10.1182/blood-2008-02-139535. This Article Full Text Full Text (PDF) Supplemental Video All Versions of this Article: blood-2008-02-139535v1 112/13/5193    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Eyles, J. L. Articles by Wicks, I. P. Search for Related Content PubMed PubMed Citation Articles by Eyles, J. L. Articles by Wicks, I. P. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES A key role for G-CSF–induced neutrophil production and trafficking during inflammatory arthritis Jo L. Eyles1,2, Michael J. Hickey3, M. Ursula Norman3, Ben A. Croker1, Andrew W. Roberts1, Sarah F. Drake1, Will G. James3, Donald Metcalf1, Ian K. Campbell1, and Ian P. Wicks1 1 The Walter and Eliza Hall Institute of Medical Research, Parkville; 2 University of Melbourne, Parkville; and 3 Centre for Inflammatory Diseases, Monash University, Victoria, Australia We have previously shown that G-CSF–deficient (G-CSF–/–) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated during CIA. Reciprocal bone marrow chimeras using G-CSF–/–, G-CSFR–/–, and wild-type (WT) mice identified nonhematopoietic cells as the major producers of G-CSF and hematopoietic cells as the major responders to G-CSF during CIA. Protection against CIA was associated with relative neutropenia. Depletion of neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically attenuated the progression of established CIA in WT mice. Intravital microscopy of the microcirculation showed that both local and systemic administration of G-CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF–induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint during CIA revealed significantly fewer adherent Gr-1+ neutrophils in G-CSF–/– mice compared with WT mice. These data confirm a central proinflammatory role for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF–induced neutrophil production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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