Eicosanoids are regulatory molecules in gamma-interferon-induced endothelial antigenicity and adherence for leucocytes.
When the endothelial cells (ECs) were stimulated with gamma-interferon (gIFN) in the presence of methylprednisolone (MP) or prostaglandin E2 (PGE2), MP enhanced gIFN-induced Ia antigen expression, whereas PGE2 inhibited it. On the other hand, while PGE2 had no effect on leucocyte binding to ECs, MP entirely inhibited it. By using selective inhibitors of the cyclo-oxygenase pathway (indomethacin, IM) and the 5-lipoxygenase pathway (L651.392), we found that addition of IM to gIFN-stimulated ECs enhanced Ia expression but had no effect on leucocyte adherence to ECs. Instead, addition of L651.392 to gIFN-stimulated ECs partially reduced leucocyte adherence to ECs but had no effect on Ia expression. Pretreatment of the ECs or leucocytes or both with monoclonal anti-class II antibody, had no effect on gIFN-induced leucocyte binding to ECs. These findings suggest that gIFN-induced endothelial cell antigenicity and leucocyte adherence are regulated independently of each other by different molecular pathways. Moreover, arachidonic acid metabolites appear to be the regulatory molecules in gIFN effects on the ECs.
Leszczynski
D
D
Transplantation Laboratory, University of Helsinki, Finland.
Häyry
P
P
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002448:Cell Adhesion; D004537:Eicosanoic Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology*; D008775:Methylprednisolone / Q000494:pharmacology; D010640:Phenothiazines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D000949:Histocompatibility Antigens Class II; D010640:Phenothiazines; D016718:Arachidonic Acid; D007371:Interferon-gamma; C053726:4-bromo-2,7-dimethoxy-3H-phenothiazin-3-one; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D008775:Methylprednisolone; D007213:Indomethacin