Augmentation of host defense mechanisms against tumor by sperabillin polymers, new basic peptidyl biopolymers, in mice.
Sperabillin polymers, which have been shown recently to have antitumor activity, are new basic peptidyl polymers composed of a pseudo-peptide antibiotic, sperabillin A. The polymers, HP-2 (MW 9990), AP-2 (MW 20,100) and AB-2 (MW 35,000), were found to potently activate murine peritoneal macrophages. The phagocytosis-dependent respiratory burst and Fc gamma receptor expression of peritoneal macrophages from C57BL/6 mice were enhanced after in vitro cultivation with these polymers. When HP-2, a representative of these polymers, was intraperitoneally injected into mice, the number of peritoneal exudate cells increased and phagocytosis-dependent respiratory burst and class II (I-A) antigen expression of peritoneal macrophages were augmented. These macrophages showed strong inhibitory activity against the growth of murine tumor cell lines such as EL4 lymphoma and B16 melanoma. Nitrogen oxide, tumor necrosis factor (TNF) and interleukin 1 (IL-1) might be required for this inhibitory activity. Moreover, in mice treated with HP-2, splenocyte counts also increased and non-specific killer activity of the splenocytes was augmented. These results indicate that sperabillin polymers are new macrophage activators.
Takizawa
M
M
Discovery Research Laboratories II, Takeda Chemical Industries Ltd, Osaka, Japan.
Hida
T
T
Harada
S
S
Tanida
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000578:Amidines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001704:Biopolymers; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D010529:Peritoneal Cavity / Q000166:cytology; D016897:Respiratory Burst / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000578:Amidines; D000900:Anti-Bacterial Agents; D001704:Biopolymers; C073529:sperabillin A