Smith R J, Sam L M, Justen J M, Bundy G L, Fitzpatrick F A, Wynalda M A
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Biochem Biophys Res Commun. 1987 Oct 29;148(2):636-45. doi: 10.1016/0006-291x(87)90924-7.
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.
人多形核中性粒细胞(PMN)暴露于源自人单核细胞的中性粒细胞激活因子(NAF)会导致颗粒成分呈浓度依赖性的细胞外释放。NAF还诱导PMN生成5(S),12(R)-二羟基-6,14-顺式-8,10-反式-二十碳四烯酸[白三烯B4(LTB4)],在外源性花生四烯酸(AA)存在的情况下这种生成会增强。与它对LTB4产生的增强作用相反,AA抑制NAF刺激的PMN脱颗粒。15(S)-羟基-5,8,11-顺式-13-反式-二十碳四烯酸(15-HETE)是AA在PMN中经15-脂氧合作用产生的产物,它会对与NAF接触的PMN的脱颗粒和LTB4生成产生浓度依赖性的抑制作用。15-HETE还抑制在NAF激活的PMN中观察到的胞质游离钙[(Ca2+)i]升高。这些数据表明,AA和一种15-脂氧合酶产物调节人PMN中与NAF相关的激活途径。