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• W2092154530 endingPage "1462" @default.
• W2092154530 startingPage "1461" @default.
• W2092154530 abstract "Leukocytic inflammation can be limited by inhibiting selectin-dependent leukocyte rolling. In spite of intensive efforts to develop small molecule selectin inhibitors with defined structure-activity profiles, inhibition of P-selectin-dependent leukocyte rolling in vivo by such a compound has yet to be described. We recently reported that glycosulfopeptides (GSP), modeled on the high affinity selectin ligand PSGL-1, inhibit leukocyte binding to P-selectin in vitro. Here, we have used intravital microscopy to investigate whether GSP can inhibit P-selectin-dependent leukocyte rolling in vivo. Surgical preparation of the mouse cremaster muscle for intravital microscopy induced P-selectin-dependent leukocyte rolling. Baseline rolling was recorded for 1 min followed by i.v. injection of GSP. 2-GSP-6 and 4-GSP-6 substantially reversed P-selectin-dependent leukocyte rolling, whereas control GSP, which are not fully glycosylated, did not. Inhibition of leukocyte rolling by 2- and 4-GSP-6 lasted 2-4 min. Clearance studies with 125I-labeled 4-GSP-6 demonstrated rapid reduction in its circulating levels concurrent with accumulation in urine. These data represent the first demonstration that a precisely defined structure based on a natural P-selectin ligand can inhibit P-selectin-dependent leukocyte rolling in vivo." @default.
• W2092154530 created "2016-06-24" @default.
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• W2092154530 date "2002-07-01" @default.
• W2092154530 modified "2023-10-16" @default.
• W2092154530 title "Glycosulfopeptides modeled on P‐selectin glycoprotein ligand‐1 inhibit P‐selectin‐dependent leukocyte rolling in vivo" @default.
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• W2092154530 doi "https://doi.org/10.1096/fj.02-0075fje" @default.
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