PSGL-1 regulates platelet P-selectin-mediated endothelial activation and shedding of P-selectin from activated platelets

Vandana S. Dole, Wolfgang Bergmeier, Ian S. Patten, Junichi Hirahashi, Tanya N. Mayadas, Denisa D. Wagner

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

We have previously shown that activated platelets in circulation stimulate release of endothelial Weibel-Palade bodies thus increasing leukocyte rolling in venules. P-selectin on the activated platelets mediates adhesion to leukocytes via PSGL-I and is rapidly shed into plasma. We were interested in studying the role of PSGL-1 in regulating expression and function of platelet P-selectin. We show here that PSGL-1 is critical for the activation of endothelial cells in venules of mice infused with activated platelets. The interaction of platelet P-selectin with PSGL-1 is also required for P-selectin shedding, as P-selectin was retained significantly longer on the surface of activated platelets infused into PSGL-1-/- compared to wild-type mice. The leukocyte integrin αMβ2 (Mac-1) was not required for P-selectin shedding. In addition to shedding, P-selectin can be downregulated from the platelet surface through internalization and this is the predominant mechanism in the absence of PSGL-1. We demonstrate that leukocyte-neutrophil elastase, known to cleave P-selectin in vitro, is not the major sheddase for P-selectin in vivo. In conclusion, interaction of platelet P-selectin with PSGL-1 is crucial for activation of the endothelium and Weibel-Palade body secretion. The interaction with PSGL-1 also results in rapid shedding of P-selectin thus downregulating the inflammatory potential of the platelet.

Original languageEnglish
Pages (from-to)806-812
Number of pages7
JournalThrombosis and Haemostasis
Volume98
Issue number4
DOIs
Publication statusPublished - 2007 Oct 1
Externally publishedYes

Keywords

  • Endothelial-activation
  • P-selectin
  • PSGL-1
  • Platelets
  • Shedding

ASJC Scopus subject areas

  • Hematology

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