Cancer Research 1988; 48(21): 6044-9.
Activation of mouse macrophages by alkylglycerols, inflammation products of cancerous tissues
N Yamamoto, D A St Claire Jr, S Homma, B Z Ngwenya
Alkylglycerols, inflammation products of lipids in cancerous tissues, are potent macrophage stimulating agents. Administration of small amounts (10-100 ng) of alkylglycerols to mice greatly enhanced macrophage activation for Fc-mediated ingestion activity at the 5th day posttreatment. Dose effect analysis revealed that dodecylglycerol (DDG), one of the alkylglycerols, stimulates macrophages most effectively at the dose of 100 ng/mouse. Administration of lower concentrations of a longer carbon chained alkylglycerol, sn-3-octadecylglycerol (batyl alcohol), to mice produced a similar activation of macrophages. In vitro incubation of mouse peritoneal cells with 50 ng DDG/ml efficiently stimulated macrophages for Fc-mediated ingestion activity. However, in vitro treatment of macrophages alone with DDG was unable to stimulate ingestion activity. When a mixture of macrophages and nonadherent (B and T) cells was treated with DDG, a greatly enhanced Fc-mediated ingestion was observed at about 3 h posttreatment, suggesting that nonadherent cells contributed to the activation of macrophages. Since coincubation of these cells with DDG is required for macrophage activation, stepwise stimulation processes by exchanging signaling factor(s) among these cell types were considered for the developmental mechanism of ingestion capacity of macrophages. When a conditioned medium of DDG-treated B- or T-cells was admixed with macrophages and incubated for 3 h, no significantly enhanced ingestion activity of macrophages was observed. Thus, exchange of signaling factor(s) among B- and T-cells was analyzed by transferring conditioned media of DDG-treated B- or T-cells to untreated T- or B-cells. When the resultant (treated B-cells—-untreated T-cells conditioned medium was admixed with untreated macrophages and incubated for 3 h, a markedly enhanced Fc-mediated ingestion was observed. However, no significant increase in ingestion activity was found in macrophages incubated with the treated T-cell—-untreated B-cell conditioned medium. Therefore, we concluded that DDG-treated B-cells initiated macrophage activation processes by releasing and transmitting a signaling factor(s) to T-cells, and in turn the T-cells modified the factor or produced a new factor(s) capable of the ultimate stimulation of macrophages for ingestion capability.