P-selectin-deficient mice are protected from PAF-induced shock, intestinal injury, and lethality

Xiaoming Sun, Ranna A. Rozenfeld, Xiaowu Qu, Wei Huang, F. Gonzalez-Crussi, Wei Hsueh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

In a previous study, we showed that anti-CD11b or anti-CD18 antibody markedly attenuated platelet-activating factor (PAF)-induced shock and intestinal necrosis in rats, whereas anti-P-selectin antibody was ineffective. Here we used genetically altered mice to study the mechanism of PAF in mice. We found that P-selectin-deficient mice are completely protected from the adverse effects of PAF with no mortality or intestinal injury and only mild hemoconcentration and transient hypotension. In contrast, CD18- or intercellular adhesion molecule 1 (ICAM-1)deficient mice were not protected from PAF-induced tissue injury and death. However, when ICAM-1-, but not CD18-, deficient mice were pretreated with fucoidin, the adverse effects of PAF were markedly reduced; survival was 100%, although hypotension still developed. Neutrophil-depleted mice were protected from PAF-induced intestinal injury but still developed hypotension and hemoconcentration. PAF increases peripheral blood neutrophil counts, probably by inducing granulopoiesis, since neutrophil-depleted mice still showed granulocytosis 60 min after PAF. Thus P-selectin plays an important role in PAF-induced injury in mice, and the selectins and the integrin-ICAM-1 system work in concert to mediate the inflammatory response to PAF in vivo.

Original languageEnglish (US)
Pages (from-to)G56-G61
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number1 36-1
DOIs
StatePublished - Jul 1997

Keywords

  • Adhesion molecules
  • Leukocyte adhesion
  • Platelet- activating factor
  • Selectin
  • Small intestine
  • β-integrin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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