TNF-alpha, IL-4, and IFN-gamma regulate differential expression of P- and E-selectin expression by porcine aortic endothelial cells

• Published in: The Journal of immunology (1950) 2000-03, Vol.164 (6), p.3309-3315
• Main Authors: Stocker, C J, Sugars, K L, Harari, O A, Landis, R C, Morley, B J, Haskard, D O
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - biosynthesis; Aorta; Cell Adhesion - immunology; Cells, Cultured; Cloning, Molecular; DNA, Complementary - isolation & purification; Down-Regulation - immunology; E-selectin; E-Selectin - biosynthesis; E-Selectin - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; g-Interferon; Humans; Interferon-gamma - physiology; Interleukin-1 - physiology; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - physiology; Leukocytes - immunology; Leukocytes - metabolism; Ligands; Membrane Glycoproteins - physiology; Molecular Sequence Data; P-selectin; P-Selectin - biosynthesis; P-Selectin - immunology; P-Selectin - metabolism; Swine; Time Factors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.6.3309

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.