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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-07-2329. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2002-07-2329v1 101/8/3249    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 Hicks, A. E. R. Articles by Norman, K. E. Search for Related Content PubMed PubMed Citation Articles by Hicks, A. E. R. Articles by Norman, K. E. Related Collections Phagocytes Cell Adhesion and Motility Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 3249-3256 PHAGOCYTES Recombinant P-selectin glycoprotein ligand-1 directly inhibits leukocyte rolling by all 3 selectins in vivo: complete inhibition of rolling is not required for anti-inflammatory effect Anne E. R. Hicks, Sarah L. Nolan, Victoria C. Ridger, Paul G. Hellewell, and Keith E. Norman From the Cardiovascular Research Group, University of Sheffield, Sheffield, United Kingdom. Selectin-dependent leukocyte rolling is one of the earliest steps of an acute inflammatory response and, as such, contributes to many inflammatory diseases. Although inhibiting leukocyte rolling with selectin antagonists is a strategy that promises far-reaching clinical benefit, the perceived value of this strategy has been limited by studies using inactive, weak, or poorly characterized antagonists. Recombinant P-selectin glycoprotein ligand-1-immunoglobulin (rPSGL-Ig) is a recombinant form of the best-characterized selectin ligand (PSGL-1) fused to IgG, and is one of the best prospects in the search for effective selectin antagonists. We have used intravital microscopy to investigate the ability of rPSGL-Ig to influence leukocyte rolling in living blood vessels and find that it can reduce rolling dependent on each of the selectins in vivo. Interestingly, doses of rPSGL-Ig required to reverse pre-existing leukocyte rolling are 30-fold higher than those required to limit inflammation, suggesting additional properties of this molecule. In support of this, we find that rPSGL-Ig can bind the murine chemokine KC and inhibit neutrophil migration toward this chemoattractant in vitro. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. W. S. Kum, S. Lee, G. A. Grassl, R. Bidshahri, K. Hsu, H. J. Ziltener, and B. B. Finlay Lack of Functional P-Selectin Ligand Exacerbates Salmonella Serovar Typhimurium Infection J. Immunol., May 15, 2009; 182(10): 6550 - 6561. [Abstract] [Full Text] [PDF] L. Almulki, K. Noda, R. Amini, A. Schering, R. C. Garland, S. Nakao, T. Nakazawa, T. Hisatomi, K. L. Thomas, S. Masli, et al. Surprising up-regulation of P-selectin glycoprotein ligand-1 (PSGL-1) in endotoxin-induced uveitis FASEB J, March 1, 2009; 23(3): 929 - 939. [Abstract] [Full Text] [PDF] J. Bestebroer, K. P. M. van Kessel, H. Azouagh, A. M. Walenkamp, I. G. J. Boer, R. A. Romijn, J. A. 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[Abstract] [Full Text] [PDF] P. R. Mangan, D. O'Quinn, L. Harrington, C. S. Bonder, P. Kubes, D. F. Kucik, D. C. Bullard, and C. T. Weaver Both Th1 and Th2 Cells Require P-Selectin Glycoprotein Ligand-1 for Optimal Rolling on Inflamed Endothelium Am. J. Pathol., December 1, 2005; 167(6): 1661 - 1675. [Abstract] [Full Text] [PDF] R. S. Scotland, M. Cohen, P. Foster, M. Lovell, A. Mathur, A. Ahluwalia, and A. J. Hobbs C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression PNAS, October 4, 2005; 102(40): 14452 - 14457. [Abstract] [Full Text] [PDF] M. D. Morgan, L. Harper, X. Lu, G. Nash, J. Williams, and C. O. S. Savage Can neutrophils be manipulated in vivo? Rheumatology, May 1, 2005; 44(5): 597 - 601. [Full Text] [PDF] J. S. Merzaban, J. Zuccolo, S. Y. Corbel, M. J. Williams, and H. J. Ziltener An Alternate Core 2 {beta}1,6-N-Acetylglucosaminyltransferase Selectively Contributes to P-Selectin Ligand Formation in Activated CD8 T Cells J. Immunol., April 1, 2005; 174(7): 4051 - 4059. [Abstract] [Full Text] [PDF] V. C. Ridger, P. G. Hellewell, and K. E. Norman L- and P-Selectins Collaborate to Support Leukocyte Rolling in Vivo When High-Affinity P-Selectin-P-Selectin Glycoprotein Ligand-1 Interaction Is Inhibited Am. J. Pathol., March 1, 2005; 166(3): 945 - 952. [Abstract] [Full Text] [PDF] M. Martinez, M. Joffraud, S. Giraud, B. Baisse, M. P. Bernimoulin, M. Schapira, and O. Spertini Regulation of PSGL-1 Interactions with L-selectin, P-selectin, and E-selectin: ROLE OF HUMAN FUCOSYLTRANSFERASE-IV AND -VII J. Biol. Chem., February 18, 2005; 280(7): 5378 - 5390. [Abstract] [Full Text] [PDF] A. E. R. Hicks, K. B. Abbitt, P. Dodd, V. C. Ridger, P. G. Hellewell, and K. E. 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