Schröder J M
Department of Dermatology, University of Kiel, Federal Republic of Germany.
J Exp Med. 1989 Sep 1;170(3):847-63. doi: 10.1084/jem.170.3.847.
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.
脂多糖（LPS）和丝裂原刺激的单核细胞分泌一种细胞因子，该细胞因子能够激活多形核白细胞（PMNL）的花生四烯酸-5-脂氧合酶。已证明这种细胞因子与最近鉴定的新型中性粒细胞激活肽NAP/IL-8相同。在存在外源性花生四烯酸（AA）的情况下，NAP/IL-8能够激活人PMNL释放白三烯B4（LTB4）、ω-氧化LTB4和5-羟二十碳四烯酸（5-HETE）。已发现释放LTB4的NAP/IL-8半数最大浓度接近4×10⁻⁸摩尔/升。时间进程研究显示PMNL迅速被激活，在最初10分钟内LTB4释放达到最大值，随后下降直至40分钟。在此期间检测到大量的ω-氧化LTB4。只有当PMNL在存在外源性AA的情况下用NAP/IL-8刺激时，才能检测到大量的AA-5-脂氧合酶产物。已发现释放半数最大LTB4所需的AA浓度为3×10⁻⁶摩尔/升。在存在8×10⁻⁹摩尔/升[³H]AA的情况下，NAP/IL-8（10⁻⁹至10⁻⁷摩尔/升）不会诱导LTB4、ω-氧化LTB4或5-HETE的产生。此外，用[³H]AA预标记的PMNL在用NAP/IL-8（10⁻⁹至10⁻⁷摩尔/升）刺激时，既不释放[³H]AA也不释放5-脂氧合酶代谢产物，这表明NAP/IL-8显然不会激活细胞磷脂酶/二酰基甘油脂肪酶。除了甲酰甲硫氨酸-亮氨酸-苯丙氨酸（FMLP）、C5a和血小板活化因子（PAF）外，NAP/IL-8是第四种明确鉴定的能够激活PMNL-5-脂氧合酶的中性粒细胞趋化因子。在银屑病患者的皮损组织中检测到大量的NAP/IL-8、花生四烯酸以及类似LTB4的物质，这表明NAP/IL-8在通过诱导LTB4产生来放大炎症过程中可能起重要作用。
