Neutrophil microsomes biosynthesize linoleate epoxide (9, 10-epoxy-12-octadecenoate), A biological active substance

• Published in: Biochemical and biophysical research communications Vol. 152; no. 3; pp. 1310 - 1318
• Main Authors: Ozawa, Takayuki, Sugiyama, Satoru, Hayakawa, Mika, Taki, Fumio, Hanaki, Yoshihiro
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 16.05.1988; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcimycin - pharmacology; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; Chromatography, High Pressure Liquid; Dogs; Fundamental and applied biological sciences. Psychology; Gas Chromatography-Mass Spectrometry; Guinea Pigs; Humans; Linoleic Acids - biosynthesis; Microsomes - metabolism; Molecular and cellular biology; Neutrophils - ultrastructure; Rabbits; Swine; GC-MS; NADPH; Percoll; NMR; TLC; HPLC; Human; Fissipedia; Carnivora; Rodentia; HPLC chromatography; Biosynthesis; Microsome; Blood; Gas chromatography; Vertebrata; Mammalia; Guinea pig; Neutrophile; Epoxide; Dog; Mass spectrometry; Structural analysis; Peritoneum
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(88)80428-5

We demonstrated that linoleate epoxide (9,10-epoxy-12-octadecenoate) exists in human burned skin and in lung lavages in patients with adult respiratory distress syndrome. This epoxide shows a highly toxic effect on cellular function. Thus, it was given the name leukotoxin. In this communication, we reveal that neutrophils from various sources such as guinea-pig peritonea and canine or human blood biosynthesize linoleate epoxide from linoleate as a substrate. From the reaction mixture of neutrophils with linoleate, a leukotoxin isomer, 12, 13-epoxy-9-octadecenoate, and a ‘non-toxic’ hydroxy derivative of linoleate, 9-hydroxy-12-octadecenoate, were detected. Biosynthesis of leukotoxin by neutrophils was substantially enhanced by osmotic activation or by a calcium-ionophore, A 23187. Microsomes prepared from neutrophils could oxygenate linoleate to leukotoxin in the presence of NADPH. In liver or kidney microsomal reaction mixture, leukotoxin could be detected only in the presence of an epoxide hydrolase inhibitor, epoxytrichloropropane. As biosynthesis of leukotoxin was sensitive to carbon monooxide, it was concluded that cytochrome P-450 dependent monooxygenase is responsible for the biosynthesis. Elucidation of the biosynthesis pathway of leukotoxin might contribute to the treatment of diseases associated with neutrophil recruitment.