Macrophage involvement in the antitumor activity of Brucella abortus ether extract against experimental lung carcinoma metastases.

Brucella abortus (strain 456) ether extract (Bru-Pel) and B. abortus lipopolysaccharide were tested for both in vitro and in vivo macrophage activation and antitumor activity in an artificial metastasis model. Purified cultures of resting macrophages were rendered nonspecifically tumoricidal for MBL-2 lymphoblastic leukemia cells by ex posure to Bru-Pel at 1 ng/ml culture medium. Brucella lipopolysaccharide, in contrast to lipopolysaccharide ex tracted from Escherichia coli and Salmonella typhimurium, failed to activate macrophages in vitro at all concentra tions tested (1 ng/ml to 10 /ig/ml). However, Bru-Pel failed to activate macrophages from endotoxin-unresponsive C3H/HeJ mice as compared to potent activation of mac rophages from closely related but endotoxin-responsive C3H/HeN mice. Treatment i.p. of homozygous nude mice with Bru-Pel induced cytotoxic macrophages, indicating that Bru-Pel activated macrophages through a thymusindependent process. An artificial metastasis model was developed in which single-cell suspensions derived from the M109 lung carcinoma were injected i.v. into BALB/c mice, and lung lesions were quantitated after 14 and 20 days by inflation of the lungs with India ink. Only Bru-Pel strikingly inhibited tumor nodule formation and was effec tive when given either 5 days prior to or 1 day after tumor inoculation. Histopathological studies of the lungs of BruPel-treated mice revealed accumulations of macrophages surrounding the metastatic foci and arresting their devel opment. Although Bru-Pel contains endotoxin, the data demonstrate that endotoxin is apparently not the active component by which Bru-Pel activates macrophages and enhances host resistance to neoplasia.