Prostaglandin E2 from macrophages of murine splenocyte cultures inhibits the generation of lymphokine-activated killer cell activity.
The present work investigated the association between prostaglandin E2 (PGE2) from macrophages and its inhibition of murine lymphokine-activated killer (LAK) cell generation. The coculture of indomethacin with interleukin-2 (IL-2) augmented LAK cell activity in an indomethacin dose-response manner, and diminished PGE2 content in the corresponding culture supernatant in a reverse dose-response manner. The correlation between the increase in LAK cell activity and the decrease in PGE2 content was highly significant. Identical results were obtained with diclofenac. A profound inhibition of LAK cell activity by exogenous PGE2 in a dose-response manner was detected. Polyclonal anti-PGE2 antiserum augmented in a dose-dependent manner the LAK cell activity, by neutralizing PGE2 in the medium. A reduction of PGE2 content in the culture supernatant was also detected when the macrophage subpopulations were cultured and was indomethacin dose-dependent. In comparison with that of normal mouse splenocytes, the incubation of whole splenocytes of tumor-bearing mice, which contained a greater subpopulation of macrophages (24% vs. 12%), produced a greater PGE2 content and a correspondingly depressed LAK cell activity. Additionally, PGE2 reduced protein kinase C (PKC) activity along with LAK cell activity generated from macrophage-depleted T cells and natural-killer-like cells. These results overall indicate that PGE2 from macrophages in murine splenocyte cultures inhibits the LAK cell generation, and PKC may be involved in the inhibition mechanism.
Ohnishi
H
H
Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, Buffalo, N.Y.
Lin
T H
TH
Nakajima
I
I
Chu
T M
TM
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D007106:Immune Sera; D004008:Diclofenac; D011493:Protein Kinase C; D015232:Dinoprostone; D007213:Indomethacin