peptones and Lymphoma

The ability of poly I:C to activate mouse macrophages (M phi) to become tumoricidal was evaluated and compared with the ability of 2 other agents, lipopolysaccharide (LPS) and M phi-activating factor (MAF), to induce a tumoricidal state. All these agents were able to stimulate proteose-peptone-elicited M phi to kill RL male 1 tumor cells in an 18-hr 51Cr release cytotoxicity assay. High levels of cytotoxicity were obtained with concentrations as low as 1 microgram/ml of LPS or poly I:C and with 1/81 dilution of MAF. However, in the presence of reagents shown to contain less than 0.01 ng/ml of LPS by the LAL assay (LPS free), we found that poly I:C induced strong reactivity, whereas MAF was ineffective. The addition of 10 ng/ml of LPS during the stimulation period did not enhance the cytotoxicity induced by poly I:C, but it did restore MAF-induced, M phi-mediated cytotoxicity. In addition, poly I:C induced strong tumoricidal activity in resident M phi and in peritoneal exudate cells from the genetically defective C3H/HeJ mice that normally do not respond to LPS and MAF treatment. Therefore, it seems that although LPS is required as a second signal for MAF-induced cytotoxicity, such a second signal is not required for poly I:C-induced cytotoxicity. From the above results, it appears that poly I:C is a more powerful activating agent than LPS and MAF and either activates M phi via a different pathway or is effective on subpopulations of M phi that are not activated by the other agents.

Topics: Animals; Cytotoxicity, Immunologic; Female; Kinetics; Lipopolysaccharides; Lymphokines; Lymphoma; Macrophage-Activating Factors; Macrophages; Mast-Cell Sarcoma; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Peptones; Poly I-C

The present study, which was designed to further characterize the "natural" T-independent rejection of syngenetic tumours (Greenberg and Greene, 1976), has revealed the following points: (1) no detectable DBA/2 NK cell activity was demonstrated against the syngeneic tumour lines studied, and these tumours were indensitive to NK cells from high-activity strains; (2) in addition the tumour frequencies in old and young mice receiving small tumour inocula were identical, in contrast with the reported decline in NK cell activity with age, suggesting that the surveillance of small inocula of these tumours was NK-cell-independent; (3) injection of silica intraperitoneally enhanced the frequency of tumours in normal and immunodeficient AT x BM mice, suggesting that the rejection mechanism was macrophage-dependent; (4) the effects of silica injection were maximal if administered 3 days prior to tumour injection, indicating that the period of time in which the rejection mechanism must act was very limited; (5) silica markedly decreased the survival of AKR mice dying of spontaneous tumours, providing evidence that the effect of this agent was not limited to model systems but would influence the appearance of spontaneous tumours; (6) reticuloendothelial stimulants such as mycobacterium butyricum and proteose peptone decreased the tumour frequency of small tumour inocula, indicating that the effector mechanism can be stimulated; and (7) soluble tumour antigen enhanced the tumour frequency in normal and immunodeficient mice, suggesting that the specific receptor molecule of the surveillance mechanism was not thymus-dependent.

Topics: Animals; Bone Marrow Transplantation; Cytotoxicity Tests, Immunologic; Killer Cells, Natural; Lymphoma; Macrophages; Mast-Cell Sarcoma; Mice; Mice, Inbred AKR; Mice, Inbred CBA; Mice, Inbred DBA; Mycobacterium; Neoplasm Transplantation; Neoplasms, Experimental; Peptones; Silicon Dioxide; Thymectomy; Transplantation, Isogeneic