title: Simultaneous intraperitoneal administration of OK-432 and serum enhances superoxide generation from migrated polymorphonuclear leukocytes, with special emphasis on the role of complements.
abstract: Superoxide and its derived active oxygen species are responsible for the polymorphonuclear leukocyte (PMN)-mediated tumoricidal activity which is typically shown in the intraperitoneal administration of OK-432, a biological response modifier, for cancer ascites. We examined the effects of intraperitoneal administration of OK-432 with or without syngeneic serum on superoxide generation from PMNs which migrated in the peritoneal cavity using the new method of Cypridina luciferin analog-dependent chemiluminescence for the detection of superoxide. PMNs harvested from rat peritoneal cavity 6 h after the intraperitoneal administration of OK-432 (0.25KE/kg, or 2.5KE/kg) generated larger amounts of superoxide than those harvested after intraperitoneal injection of oyster glycogen (75mg/kg) when stimulated by opsonized zymosan or phorbol myristate acetate. Simultaneous intraperitoneal administration of OK-432 and syngeneic serum induced a greater increase in PMN superoxide generation than OK-432 alone, which was reversed by a complement activation inhibitor (MX-1). Simultaneous injection of OK-432 and heat-inactivated syngeneic serum did not exhibit a significant increase in PMN superoxide generation as compared with OK-432 alone. These results provide pharmacological evidence to the satisfactory therapeutic effects of the intraperitoneal administration of OK-432 with or without serum for patients with cancer ascites, and indicate that complements, in particular C5a, are involved in this enhanced PMN-derived superoxide generation induced by the simultaneous injection of OK-432 and serum.
authors.affiliation: First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Kondo
mesh_terms: D000818:Animals; D016913:Blood Component Transfusion; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology*; D007274:Injections, Intraperitoneal; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010844:Picibanil / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D013481:Superoxides; D010844:Picibanil; D003165:Complement System Proteins; D013755:Tetradecanoylphorbol Acetate