Cytotoxicity of cancer patients' macrophages for tumor cells: purification and characterization of plasma inhibitory factors obtained from colon cancer patients.
Monocyte derived macrophages from breast and gynecologic cancer patients generally do not acquire enhanced cytotoxicity for human tumor cells after incubation with bacterial lipopolysaccharide (LPS) whereas the macrophages isolated from colon and hematologic cancer patients are cytotoxic. However, it was also found that 75% of the patients possessing cytotoxic macrophages also had a plasma factor which suppressed macrophage mediated cytotoxicity. The plasma inhibitory factor obtained from a colon cancer patient was purified utilizing Sephadex G-200 column chromatography and 4 fractions (A, B, C and D) with inhibitory activity, were isolated. When a plasma sample obtained from a colon cancer patient found to be lacking the inhibitor of macrophage cytotoxicity was fractionated, 2 fractions were isolated with inhibitory activity. These fractions corresponded to fractions A and C of the inhibitory sample. Pooled AB+ serum was also fractionated and no inhibitory fractions could be isolated. The inhibitory factors were further characterized and it was found that fractions A and B appear to be inhibitors of lysosomal enzyme activity and fraction C appears to be an inhibitor of protease activity. When the plasma from cancer patients known to possess an inhibitor of macrophage mediated cytotoxicity was examined for the presence of fraction A, B, C and D, it was found that every colon cancer patient studied possessed inhibitors A, B, C and D. Breast cancer patients possessed some combination of A, B and C but all lacked fraction D and the gynecologic cancer patients possessed some combination of factors A, B and D but they all lacked inhibitor C.
D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology; D002850:Chromatography, Gel; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005833:Genital Neoplasms, Female / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000032:analysis / Q000302:isolation & purification*; D007108:Immune Tolerance; D007163:Immunosorbent Techniques; D007938:Leukemia / Q000276:immunology; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000276:immunology*; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000302:isolation & purification; D011817:Rabbits
D007106:Immune Sera; D011480:Protease Inhibitors; C029764:antimacrophage globulin