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, IL-4, and IFN-
Regulate Differential Expression of P- and E-Selectin Expression by Porcine Aortic Endothelial Cells1


*
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.
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