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The Journal of Immunology, 2000, 164: 3309-3315.
Copyright © 2000 by The American Association of Immunologists

TNF-{alpha}, IL-4, and IFN-{gamma} Regulate Differential Expression of P- and E-Selectin Expression by Porcine Aortic Endothelial Cells1

Claire J. Stocker*, Katharine L. Sugars*, Olivier A. Harari*, R. Clive Landis{dagger}, Bernard J. Morley{dagger} and Dorian O. Haskard2,*

* British Heart Foundation Cardiovascular Medicine Unit, and {dagger} Department of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom

P- and E-selectin are surface glycoproteins that mediate leukocyte rolling on the surface of endothelium in inflammation. We have cloned porcine P-selectin cDNA and generated a mAb, 12C5, with which to examine P-selectin expression by porcine aortic endothelial cells (PAEC) in comparison with that of E-selectin. Basal expression by PAEC of P-selectin was greater than that of E-selectin, whereas E-selectin expression was more prominently enhanced than that of P-selectin by stimulation with TNF-{alpha} or IL-1{alpha}. Both human or porcine IL-4 led to an increase in P-selectin expression, with kinetics that were delayed compared with those seen following stimulation with TNF-{alpha} or IL-1{alpha}, but IL-4 did not stimulate expression of E-selectin. When cells were stimulated with TNF-{alpha} in the presence of IL-4, we observed enhanced P-selectin expression with a parallel reduction in E-selectin expression. Finally, the increase in P-selectin expression due to human IL-4 was reduced in the presence of porcine but not human IFN-{gamma}. These observations show that E-selectin and P-selectin expression are differentially regulated in PAEC, and that IL-4 leads to a shift in the relative surface density of the two molecules toward P-selectin. The ability of porcine IFN-{gamma} to inhibit IL-4-induced P-selectin expression suggests that the balance between Th1 and Th2 cytokine production may determine the relative densities of the two selectins in chronic immune-mediated inflammation. Because the increased expression of P-selectin induced by human IL-4 was not inhibited by human IFN-{gamma}, this balance may be shifted toward P-selectin expression in porcine xenografts infiltrated by human lymphocytes.




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