Tumor necrosis factor induces E-selectin production in splanchnic artery occlusion shock.
Splanchnic arteries were clamped for 45 min to induce splanchnic artery occlusion (SAO) shock in anesthetized rats. Sham-operated animals were used as controls. Survival time, serum tumor necrosis factor-alpha (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure, myeloperoxidase (MPO) activity, and serum levels of soluble E-selectin (sE-selectin) were investigated. SAO-shocked rats exhibited decreased survival time (95 +/- 11 min, whereas sham-shocked rats survived for > 5 h), reduced mean arterial blood pressure, increased serum levels of TNF-alpha (185 +/- 8 U/ml) and MPO activity in the ileum (0.11 +/- 0.03 U x 10(-3)/g tissue) and lung (1.5 +/- 0.4 U x 10(-3)/g tissue), leukopenia, and enhanced serum levels of sE-selectin. Furthermore SAO-shocked rats showed histological alterations in the ileum and lung. Administration of cloricromene (2 mg/kg i.v.), an inhibitor of TNF-alpha, significantly increased survival time (225 +/- 10 min), decreased serum levels of TNF-alpha and sE-selectin, reduced leukopenia and MPO activity in the ileum (0.035 +/- 0.003 U x 10(-3)/g tissue) and lung (0.3 +/- 0.005 U x 10(-3)/g tissue), improved the cardiovascular changes, and reduced the histological changes in the ileum and lung. Finally, an anti-E-selectin antibody protected rats against SAO shock. Our findings are consistent with an involvement of E-selectin, "in vivo," in the pathogenesis of SAO shock.
Altavilla
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Institute of Pharmacology, School of Medicine, University of Messina, Italy.
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Ioculano
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AP
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000473:pathology; D001794:Blood Pressure; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000097:blood; D002866:Chromonar / Q000031:analogs & derivatives / Q000494:pharmacology; D019040:E-Selectin; D007958:Leukocyte Count; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000378:metabolism* / Q000473:pathology; D013152:Splanchnic Circulation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; C025945:cloricromen; D002866:Chromonar