Suppression of macrophage function by substances with a molecular weight lower than 3000 Da in B16 melanoma-conditioned medium.
In the present study, B16 melanoma cells were found to produce inhibitory and cytotoxic substances with a molecular weight lower than 3000 Da against macrophages in a conditioned medium. The B16 melanoma-conditioned medium suppressed nitric oxide (NO) production only by mouse peritoneal macrophages and the mouse macrophage-like cell line, RAW264.7 cells, but not by rat peritoneal macrophages. In addition, it showed cytotoxicity against mouse peritoneal macrophages and mouse macrophage-like cell lines, RAW264.7 and J774A.1 cells, but not against rat cells (peritoneal macrophages, 3Y1, hepatocytes), human cells (HeLa, KB, MCF-7), or mouse 3T3-L1 cells. The inhibitory activity of NO production was not affected by trypsin treatment or arginine supplementation, but it was abolished by heat treatment at 95 degrees C for 3 min. On the other hand, the cytotoxicity was not influenced by these treatments. Inducible NO synthase induction following lipopolysaccharide stimulation was reduced by treatment of mouse peritoneal macrophages with B16 melanoma-conditioned medium. These results suggest that metastatic B16 melanoma cells produce two distinct substances: to suppress NO production by macrophages and to kill macrophages and macrophage-like cell lines. We propose that these activities may help metastatic B16 melanoma cells to escape a host immunosurveillance system and to metastasize to target organs.
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. inoue@phar.nagoya-cu.ac.jp
Makoto
M
Inoue
Takamasa
T
Ohno
Yukio
Y
Ogihara
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D017077:Culture Media, Conditioned; D009569:Nitric Oxide