Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes.
Trihydroxytetraenes, a novel series of oxygenated derivatives formed from arachidonic acid in human leukocytes, were recently isolated [Serhan, C. N., Hamberg, M. & Samuelsson, B. (1984) Biochem. Biophys. Res. Commun. 118, 943-949]. The structure of the major compound was established--i.e., 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid. The present study reports the structure of a second member of the trihydroxytetraene series of compounds--i.e., 5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid. When added to human neutrophils, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid stimulated superoxide anion generation and degranulation at submicromolar concentrations without provoking a substantial aggregation response. With respect to superoxide anion generation, 5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid proved to be as potent as leukotriene B4. In contrast, the compound was approximately 2 orders of magnitude less potent than either leukotriene B4 or fMet-Leu-Phe at provoking degranulation. The results indicate that interaction(s) between the 5- and 15-lipoxygenase pathways of human leukocytes leads to formation of a new series of oxygenated derivatives of arachidonic acid that may be involved in regulating specific cellular responses. The trivial names lipoxin A (5,6,15L-trihydroxy-7,9,11,13-icosatetraenoic acid) and lipoxin B (5D,14,15L-trihydroxy-6,8,10,12-icosatetraenoic acid) are proposed for the new compounds.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D044045:Lipoxins; D013058:Mass Spectrometry; D009504:Neutrophils / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood; D013056:Spectrophotometry, Ultraviolet; D013481:Superoxides / Q000097:blood
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D013481:Superoxides; D016718:Arachidonic Acid; D000001:Calcimycin; C042651:lipoxin B4; D010196:Pancreatic Elastase