Journal of Leukocyte Biology 37:63-73 (1985) Enhanced Lysis of (1251]5-Iodo-2’- Deoxyuridine-Labeled Target Cells in the Presence of Normal Macrophages: Possible Mechanisms of Action

The potential mechanisms involved during the faster release of [125l].iodo-2’. deoxyuridine (125ldUrd)-labeled target sarcoma cells in the presence of normal C57BLJ6J peritoneal macrqphages were investigated. Maximum ( = 90%) “spontaneous ” release of 12b1 from target cells cultured alone occurred over a period of about 10 days. However, after about 3 days, confluent sheets of target cells developed. In the presence of normal macrophages, 90 % of the 1251 was released between 3 and 7 days, again with the formation of confluent sheets of target cells. This enhanced 12l release was not influenced by increasing the relative concentration of IdUrd using the nonradioactive isotope 127ldUrd. Established mechanisms of target cell destruction were investigated but no evidence was found for the involvement of superoxide anion, hydrogen peroxide, or regulation by prostaglandmn synthesis. The macrophage-mediated effect was abrogated by incorporating hydrocortisone-acetate (10w to iO M) into the culture medium but this did not affect target cell proliferation. The use of serum-free culture medium suggested that macrophages secreted a soluble mediator that was not derived from or dependent on the presence of fetal bovine serum. In addition, macrophage-conditioned medium was able to induce the faster 1251 release. The failure to precipitate with 20 % trichloroacetic acid the 1251 released from target cells cultured in the presence of macro-phages indicated that the radioactive component had been separated from the precipitable DNA. The data are discussed in light of two possible hypotheses: that macrophages recognized subtle changes in IdUrd-labeled cells and exac-erbate radiotoxicity, and that the faster release reflected proliferative death caused by stimulated growth