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Soluble P‐Selectin Antagonist Mediates Rolling Velocity and Adhesion of Leukocytes in Acutely Inflamed Venules
Author(s) -
EPPIHIMER MICHAEL J.,
SCHAUB ROBERT G.
Publication year - 2001
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2001.tb00154.x
Subject(s) - intravital microscopy , selectin , inflammation , extravasation , venule , cell adhesion molecule , adhesion , p selectin , cd18 , cell adhesion , chemistry , cd11c , immunology , medicine , integrin alpha m , receptor , microcirculation , biochemistry , platelet , platelet activation , organic chemistry , gene , phenotype
Objective : Leukocyte rolling is recognized as an important event in facilitating the extravasation of leukocytes from the vascular to the interstitial compartment, and is mediated by the selectin family of cell adhesion molecules. The aim of this study was to evaluate and characterize the rolling behavior of leukocytes in a model of acute inflammation using a novel soluble selectin ligand directed against P‐selectin. Methods : Feline mesenteric postcapillary venules were visualized using intravital microscopy prior to and following exposure to leukotriene C 4 (LTC 4 ) in animals pretreated with vehicle (saline) and the P‐selectin antagonist rPSGL‐Ig. Results : A concentration of 500 pM LTC 4 induced a threefold and sixfold elevation in leukocyte rolling flux and adhesion, respectively, compared to baseline values ( p < 0.05). Administration of rPSGL‐Ig had no effect on LTC 4 ‐induced leukocyte rolling flux but significantly attenuated the increase in the fraction of rolling leukocytes ( p < 0.05). In addition, rPSGL‐Ig inhibited the LTC 4 ‐induced reductions in leukocyte rolling velocity ( p < 0.001). Finally, LTC 4 ‐induced leukocyte adhesion in animals pretreated with rPSGL‐Ig was reduced by 60%, compared to vehicle‐treated animals ( p < 0.05). Conclusions : LTC 4 induces leukocyte rolling and adhesion in feline mesenteric venules in a dose‐dependent manner. Administration of rPSGL‐Ig inhibits LTC 4 ‐induced reductions in leukocyte rolling velocity and attenuates the elevation in the fraction of rolling leukocytes produced by LTC 4 stimulation. This suggests that rPSGL‐Ig may be used to reduce leukocyte rolling and adhesion, and subsequently attenuate tissue injury during inflammation.