TNF-alpha, IL-4, and IFN-gamma regulate differential expression of P- and E-selectin expression by porcine aortic endothelial cells.
J Immunol
; 164(6): 3309-15, 2000 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-10706724
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-1alpha. 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-1alpha, 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Interleucina-4
/
Interferon gama
/
Fator de Necrose Tumoral alfa
/
Selectina-P
/
Selectina E
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Reino Unido