PRODUCTION OF AN ANTI-TUMOR CYTO-TOXIN BY HUMAN-MONOCYTES

Abstract

Human monocytes incubated in vitro for 20 h at 37.degree. C release a factor which is cytotoxic to a number of human and murine tumor cell lines; untransformed cells appear to be less susceptible. A similar factor is produced under comparable conditions by myelomonocytic leukemic cells and by macrophages derived from monocytes by in vitro culture for 8 days. Maximum production of the factor occurred in the presence of fetal calf serum or autologous plasma and endotoxin. The factor is newly synthesized in culture as its production is reduced if the monocytes are treated with cycloheximide or actinomycin D or incubated at lower temperatures. Freshly isolated monocytes do not release the factor on freeze-thaw or hypotonic lysis. The monocyte cytotoxin has apparent MW of 34,000 on Ultrogel AcA54 gel filtration and 140,000 on gradient polyacrylamide gel electrophoresis; it has .beta.2-.gamma.1 electrophoretic mobility in polyacrylamide gel and does not appear to be C3a [complement component 3a] or arginase.