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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 (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 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 Articles by Norman, K. E Search for Related Content PubMed PubMed Citation Articles by Hicks, A. E Articles by Norman, K. E Social Bookmarking                   What's this? Submitted August 1, 2002 Accepted November 12, 2002 Recombinant P-Selectin Glycoprotein Ligand-1 directly inhibits leukocyte rolling by all three selectins in vivo: Complete inhibition of rolling is not required for anti-inflammatory effect Anne E Hicks, Sarah L Nolan, Victoria C Ridger, Paul G Hellewell, and Keith E Norman* Cardiovascular Research Group, University of Sheffield, Sheffield, South Yorkshire, United Kingdom * Corresponding author; email: k.norman{at}shef.ac.uk. 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 characterised antagonists. rPSGL-Ig is a recombinant form of the best characterised 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 towards this chemoattractant in vitro. 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