BRM activities of low-toxic Bordetella pertussis lipopolysaccharides.
A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
Abe
S
S
Teikyo University School of Medicine, Tokyo, Japan.
Ohnishi
M
M
Kimura
S
S
Yamazaki
M
M
Oshima
H
H
Mizuno
D
D
Yamaguchi
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001886:Bordetella pertussis; D002448:Cell Adhesion; D007155:Immunologic Factors / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy; D009504:Neutrophils / Q000166:cytology
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D008070:Lipopolysaccharides