Modulation of P-selectin expression in the postischemic intestinal microvasculature.
The dual radiolabeled monoclonal antibody technique was used to 1) define the magnitude and kinetics of P-selectin expression in murine small intestine exposed to ischemia-reperfusion (I/R), and 2) determine the factor(s) responsible for initiating this response. Within 10 min after release of a 20-min arterial occlusion, intestinal P-selectin expression increased two- to threefold compared with control values. Peak (4-fold) expression of P-selectin was noted at 5 h after reperfusion, returning to the control value at 24 h. The early (10-30 min) I/R-induced upregulation of P-selectin appears to reflect mobilization of a performed pool of the adhesion molecule, whereas the later (5 h) rise appears to be transcription dependent. The early increase in P-selectin expression was not inhibited by pretreatment with either oxypurinol (inhibits xanthine oxidase), diphenhydramine (H1-receptor antagonist), or MK-571 (leukotriene C4/D4 antagonist), nor was it blunted in transgenic mice expressing three times the normal level of copper-zinc superoxide dismutase or in mast cell-deficient mice. However, significant inhibition was noted after treatment with either MK-886 (5-lipoxygenase inhibitor) or a nitric oxide (NO) donor (diethylenetriamine/NO). These findings indicate that the early I/R-induced increase in intestinal P-selectin expression is mediated by a 5-lipoxygenase-dependent NO-inhibitable mechanism.
Eppihimer
M J
MJ
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Russell
J
J
Anderson
D C
DC
Epstein
C J
CJ
Laroux
S
S
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D004155:Diphenhydramine / Q000494:pharmacology; D007421:Intestine, Small / Q000098:blood supply* / Q000378:metabolism*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008833:Microcirculation / Q000502:physiology*; D010117:Oxypurinol / Q000494:pharmacology; D019007:P-Selectin / Q000096:biosynthesis*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015424:Reperfusion; D013152:Splanchnic Circulation / Q000502:physiology*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D011422:Propionates; D011804:Quinolines; C059141:verlukast; D004155:Diphenhydramine; D013482:Superoxide Dismutase; D010117:Oxypurinol