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

Am J Physiol. 1997 Jul;273(1 Pt 1):G56-61. doi: 10.1152/ajpgi.1997.273.1.G56.

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 anti-body 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • CD18 Antigens / physiology
  • Death
  • Hypotension / chemically induced
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology
  • Intestine, Small / pathology
  • Intestines / drug effects
  • Intestines / pathology*
  • Leukocyte-Adhesion Deficiency Syndrome / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Necrosis
  • P-Selectin / genetics
  • P-Selectin / physiology*
  • Platelet Activating Factor / antagonists & inhibitors
  • Platelet Activating Factor / toxicity*
  • Polysaccharides / pharmacology
  • Rats
  • Shock / physiopathology*
  • Shock / prevention & control
  • Species Specificity

Substances

  • Anticoagulants
  • CD18 Antigens
  • P-Selectin
  • Platelet Activating Factor
  • Polysaccharides
  • Intercellular Adhesion Molecule-1
  • fucoidan