HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stocker, C. J. Articles by Haskard, D. O. Search for Related Content PubMed PubMed Citation Articles by Stocker, C. J. Articles by Haskard, D. O.

TNF-, IL-4, and IFN- 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, Bernard J. Morley and Dorian O. Haskard^2,*

^* British Heart Foundation Cardiovascular Medicine Unit, and 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- or IL-1. 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- or IL-1, but IL-4 did not stimulate expression of E-selectin. When cells were stimulated with TNF- 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-. 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- 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-, this balance may be shifted toward P-selectin expression in porcine xenografts infiltrated by human lymphocytes.