Regulation of mitogen- and TCGF-induced lymphocyte blastogenesis by prostaglandins and supernatant from equine embryos and endometrium.
Immunosuppressive substances which interfere with lymphocyte blastogenesis are released in vitro by embryos and endometrium from mares in early pregnancy. Immunosuppression was not evident when tissues were cultured in the presence of indomethacin (a prostaglandin-synthesis inhibitor). Various prostaglandins (PGs) were added to equine lymphocytes and lymphocyte proliferation was measured after the addition of concanavalin A (Con A) or phytohaemagglutinin A (PHA). PGE2 and PGF2 alpha inhibited Con A-induced blastogenesis down to final concentrations of 1.8 x 10(-9) M and 1.3 x 10(-6) M, respectively. Other PGs tested (6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGF2 alpha) did not affect Con A-induced blastogenesis. PHA-induced blastogenesis was inhibited by concentrations down to 1.8 x 10(-9) M PGE2, 3.3 x 10(-7) M PGF2 alpha and 2.8 x 10(-4) M 6-keto-PGF1 alpha. At all concentrations, 13,14-dihydro-15-keto-PGF2 alpha only slightly reduced PHA-induced blastogenesis. Therefore, PGE2 was the only prostaglandin tested which, at physiological concentrations, significantly inhibited incorporation of [3H] thymidine. The mechanism of PGE2-mediated suppression was studied by adding PGE2 and T cell growth factors (TCGF) to TCGF-responsive lymphocytes. PGE2 reduced the TCGF-mediated blastogenic response in a dose-dependent manner. Furthermore, culture supernatant from embryos and endometrium from 14-day pregnant mares inhibited lymphocyte blastogenesis induced by TCGF. These results show that PGE2 interferes with lymphocyte blastogenesis by TCGF-dependent mechanisms. It is suggested that the PGE2 present in the uterus of the early pregnant mare may be one of the factors involved in immunosuppression at the time of maternal recognition of pregnancy.
Watson
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ED
Section of Reproductive Studies, University of Pennsylvania, New Bolton Center, School of Veterinary Medicine, Kennett Square 19348.
Zanecosky
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HG
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D015237:Dinoprost / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D004717:Endometrium / Q000276:immunology*; D005260:Female; D006736:Horses / Q000196:embryology / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D011453:Prostaglandins / Q000276:immunology*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D011453:Prostaglandins; D003208:Concanavalin A; D015237:Dinoprost; D015232:Dinoprostone