Macrophage-derived prostaglandin E modulation of the mixed-lymphocyte reaction: an anomaly of increased production and decreased T-cell susceptibility during tumor growth.
One-way mixed-lymphocyte reactions (MLR) were used to assess macrophage (M phi)-derived factor-mediated modulation of normal and tumor-bearing host (TBH) T-cell immune responsiveness. Normal and TBH M psi culture supernatants contained the inhibitory substance prostaglandin E (PGE) in concentrations of 10(-8) to 10(-9) M, with TBH M phi supernatant containing approximately twice the amount of PGE as its normal counterpart. Normal and TBH MLR reactivity were both suppressed by the addition of normal host M phi supernatant. However, TBH T cells were less inhibited by TBH M phi supernatant (55%) as compared to normal host T cells (73%). Although dialyzed M phi supernatants were less inhibitory (17-19%) on normal host T-cell MLR reactivity, TBH T-cell responses were enhanced (20-46%). Indomethacin or eicosatetraynoic acid treatment of M phi reduced PGE levels in the supernatants and in general enhanced MLR reactivity. When PGE1 and PGE2 were titrated in the MLR, normal host T lymphocytes were more susceptible to inhibition than were TBH. Concentrations of PGE1 and PGE2 comparable to that found in normal host M phi supernatants caused approximately 38% inhibition whereas whole M phi supernatants decreased MLR reactivity by greater than 70%, suggesting that another factor(s) was necessary to account for the additional M phi-mediated suppression of lymphocyte function. Isoelectric focusing was used to fractionate normal host M phi supernatant. Two factors with isoelectric points in the pH ranges 7.0-8.5 and 4.5-5.0 were inhibitory in the MLR. An enhancing factor was also identified with an pI in the range of pH 6.0-7.0. These data suggest that TBH M phi-derived PGE production was increased over its normal counterpart, but that TBH T cells were less susceptible to its effect and an additional factor(s) was working in concert with PGE.
D000818:Animals; D015232:Dinoprostone; D005354:Fibrosarcoma / Q000276:immunology*; D007108:Immune Tolerance; D007525:Isoelectric Focusing; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D011458:Prostaglandins E; D015232:Dinoprostone