Differential stimulation of macrophages for tumor cytostasis and monokine production.
We have investigated whether antitumor activity could be expressed independently of cytokine production. Resident macrophages treated with interferon-gamma (IFN-gamma), lipopolysaccharide (LPS) plus muramyldipeptide (MDP) expressed a cytostatic activity against P815 tumor cells and released interleukin 6 (IL-6) and nitrite but produced neither IL-1 nor tumor necrosis factor (TNF). Thioglycollate-elicited macrophages required only LPS plus IFN-gamma for cytostatic activity which was expressed concomitantly with the release of high levels of TNF, IL-1 and IL-6, whereas C3H/HeJ macrophages produced low levels of monokines and were not cytostatic. LPS, alone, was sufficient for triggering Concanavalin A-primed macrophages leading to a full cytostatic activity, even in C3H/HeJ macrophages that was expressed, for these latter, in the absence of monokine production. TNF did not appear to play a role either in autocrine stimulation of macrophages or in the cytostatic process because anti-TNF antiserum affected neither the cytostatic activity nor the nitrite production.
Sarih
M
M
C.N.R.S. URA 1116, Institut de Biochimie, Université Paris-Sud, Orsay, France.
Souvannavong
V
V
Adam
A
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D012515:Mast-Cell Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D015846:Monokines / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000970:Antineoplastic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015846:Monokines; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma