Suppression of polyclonal, tumor cell and alloantigen-induced proliferation: identification of cyclooxygenase pathway dependent and independent mechanisms.
Polyclonal T cell activation, syngeneic tumor cell and alloantigen-induced proliferative responses were studied to determine if the regulation of these responses in normal and tumor-bearing NBR rats is mediated through products of the cyclooxygenase pathway and prostaglandin E2 (PGE2) in particular. Young rats and tumor-bearing rats have previously been shown to produce poor proliferative responses to PHA, Con A and syngeneic methylcholanthrene (MCA)-induced fibrosarcoma cells. The poor responses to PHA and Con A are mediated by PGE2 in unfractionated ( UNF ) and nylon wool adherent (ADH) cells. The same relationship was also established in the mixed leukocyte tumor cell (MLTC) response to MCA tumor cells although it appears to be of only minor significance as the enhancement following indomethacin (IND) treatment is still a relatively poor response. Indomethacin generally had no effect on the proliferative responses of tumor-bearing animals indicating that the suppression was not mediated through the cyclooxygenase pathway. We have also extended a previous observation in which UNF cells were found to be unresponsive to alloantigen stimulation. This suppression does not appear to be mediated through cyclooxygenase products as IND treatment does not enhance the UNF response although it does enhance the ADH response. These data indicate that a complex network of cyclooxygenase dependent and independent regulation exists in normal and tumor-bearing NBR rats.
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D005354:Fibrosarcoma / Q000276:immunology*; D007108:Immune Tolerance; D007213:Indomethacin / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008934:Mitogens / Q000494:pharmacology; D009368:Neoplasm Transplantation; D011458:Prostaglandins E / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D016861:Cyclooxygenase Inhibitors; D007519:Isoantigens; D008934:Mitogens; D011458:Prostaglandins E; D012459:Salicylates; D015232:Dinoprostone; D020156:Salicylic Acid; D007213:Indomethacin