Arachidonic acid and 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid modulate human polymorphonuclear neutrophil activation by monocyte derived neutrophil activating factor.
Exposure of human polymorphonuclear neutrophils (PMN) to human monocyte derived neutrophil activating factor(s) (NAF) resulted in a concentration-dependent extracellular release of granule constituents. NAF also induced the generation of 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid [Leukotriene B4 (LTB4)] by PMNs which was enhanced in the presence of exogenous arachidonic acid (AA). In contrast to its enhancing effect on LTB4 production, AA inhibited NAF-stimulated PMN degranulation. 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE), a product of the 15-lipoxy-genation of AA in PMNS, caused a concentration-dependent suppression of degranulation and LTB4 generation by PMNs in contact with NAF. 15-HETE also inhibited the rise in cytosolic-free calcium [( Ca2+]i) observed in NAF activated PMNs. These data suggest that AA and a 15-lipoxygenase product modulate the NAF-associated activation pathway in human PMNs.
Smith
R J
RJ
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Sam
L M
LM
Justen
J M
JM
Bundy
G L
GL
Fitzpatrick
F A
FA
Wynalda
M A
MA
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001688:Biological Products / Q000302:isolation & purification / Q000502:physiology*; D016207:Cytokines; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000097:blood; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D001688:Biological Products; D016207:Cytokines; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid