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Augmentation of Release of Cytotoxin from Murine Bone Marrow and Peritoneal Macrophages by Tumor Transplantation¹

Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui-gun, Kanagawa 199-01, Japan

Cytotoxin release by bone marrow-adherent cells and peritoneal macrophages was transiently augmented by i.p. inoculation of syngeneic tumor cells, but not normal cells. These effects were maximal 24–48 h after tumor transplantation. The cytotoxin released from bone marrow-adherent cells obtained 24 h after tumor inoculation had a molecular weight of about 70,000. Peritoneal macrophages obtained 24 h after tumor inoculation released mainly a cytotoxin with a molecular weight of about 55,000, whereas 48-h peritoneal macrophages released both M_r 55,000 and 70,000 cytotoxins. Activities of these three cytotoxins were inhibited by the addition of rabbit anti-murine tumor necrosis factor antibody. No change in expression of antigens on cells producing the cytotoxin was detected in bone marrow-adherent cells obtained 24 h after tumor inoculation, compared to normal bone marrow-adherent cells. However, expression of surface antigens of peritoneal macrophages obtained 24 h after tumor inoculation differed from that of peritoneal macrophages obtained 48 h later. Antigen expression of 48-h peritoneal macrophages producing the cytotoxin was similar to that of 24-h bone marrow-adherent cells producing the cytotoxin. Taken together with the cytotoxin data, it appears that some cells in 48-h peritoneal macrophages may originate from 24-h bone marrow macrophages. These data suggest that the local tumor burden stimulates the central macrophages in bone marrow as well as the local macrophages and that stimulated macrophages in bone marrow may then mobilize to the local site of the tumor transplantation.

¹ Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 4/ 4/88. Revised 7/28/88. Revised 10/13/88. Accepted 10/19/88.