15-Hydroxyeicosatetraenoic acid inhibits superoxide anion generation by human neutrophils: relationship to lipoxin production.
Human neutrophils can aggregate, degranulate, and release mediators of inflammation including oxygen radicals and lipoxygenase (LO)-derived products of arachidonic acid. The regulation of 5- and 15-lipoxygenases appears to be important since their products (e.g. leukotrienes and lipoxins) display unique spectra of bioactions. Addition of 15-HETE, a product of the 15-LO, to neutrophils in suspension dramatically shifted the LO products generated and led to a dose-dependent increase in lipoxins, while the production of leukotriene B4 and its omega-oxidation products (i.e. 20-COOH-LTB4 and 20-OH-LTB4) was inhibited. Exogenous 15-HETE also dose-dependently inhibited the generation of superoxide anions induced by either the chemotactic peptide f-met-leu-phe or the divalent cation ionophore A23187. Neither lipoxin A4 nor lipoxin B4 (10(-8)-10(-6) M) inhibited O2-. generation induced by either f-met-leu-phe or A23187. These results indicate that in addition to serving as a substrate for lipoxin generation, 15-HETE also inhibits superoxide anion generation by human neutrophils. Together they provide further evidence to suggest that products of the 15-lipoxygenase may serve a regulatory role at inflammatory loci.
Serhan
C N
CN
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Reardon
E
E
D000001:Calcimycin / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D044045:Lipoxins; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D005609:Free Radicals; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D013481:Superoxides; D000001:Calcimycin; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C042651:lipoxin B4