title: The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate.
abstract: LPS and mitogen-stimulated mononuclear cells secrete a cytokine, which is able to activate the PMNL-arachidonate-5-lipoxygenase. This cytokine has been proven to be identical with the recently characterized novel neutrophil-activating peptide NAP/IL-8. NAP/IL-8 is able to activate human PMNL for release of LTB4, omega-oxidized LTB4, and 5-HETE in the presence of exogenous AA. Half-maximal concentration of NAP/IL-8 for release of LTB4 has been found to be near 4 x 10(-8) mol/liter. Time course studies revealed rapid activation of PMNL, with maximal release of LTB4 within the first 10 min with a decline up to 40 min. High amounts of omega-oxidized LTB4 were detected up to that time. Significant amounts of AA-5-LO-products can be detected only when PMNL were stimulated with NAP/IL-8 in the presence of exogenous AA. The concentration of AA necessary for half-maximal LTB4 release has been found to be 3 x 10(-6) mol/liter. In the presence of 8 x 10(-9) mol/liter [3H]AA, NAP/IL-8 (10(-9) to 10(-7) mol/liter) did not induce the production of LTB4, omega-oxidized LTB4, or 5-HETE. In addition, PMNL prelabeled with [3H]AA did not release either [3H]AA or 5-lipoxygenase metabolites when stimulated with NAP/IL-8 (10(-9) to 10(-7) mol/liter), indicating that NAP/IL-8 apparently does not activate cellular phospholipases/diacylglycerol-lipases. Apart from FMLP, C5a, and PAF NAP/IL-8 is the fourth clearly characterized neutrophil chemotaxin able to activate the PMNL-5-lipoxygenase. The detection of large amounts of NAP/IL-8, arachidonic acid, as well as LTB4-like material, in lesional material of patients with psoriasis points towards a possibly important role of NAP/IL-8 in amplifying inflammatory processes by induction of LTB4-production.
authors.affiliation: Department of Dermatology, University of Kiel, Federal Republic of Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Schröder
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002630:Chemotactic Factors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D002630:Chemotactic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D010455:Peptides; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase