Berkova N, Gilbert C, Goupil S, Yan J, Korobko V, Naccache P H
Laboratoire d'endocrinologie de la reproduction and Unité de recherche en genétique humaine et moléculaire, Centre de recherche de St-Françoise d'Assise, Québec, Canada.
J Immunol. 1999 May 15;162(10):6226-32.
Haptoglobin (Hp), TNF-alpha, and neutrophils are parts of a highly interactive ensemble participating in inflammatory processes. Hp is taken up by neutrophils, stored within a cytoplasmic granular compartment, and is secreted during phagocytosis by those cells. In the present study, the effects of TNF-alpha on the release of Hp from human neutrophils were investigated. Incubation of neutrophils with TNF-alpha induced the release of Hp from cells in a time- and concentration-dependent manner as revealed by Western blot analysis and immunofluorescence. The release of Hp induced by TNF-alpha was not due to nonspecific lysis of the cells. TNF-alpha is a highly pleiotropic cytokine that mediates its effects by binding to two distinct receptors (p55 and p75). Administration of TNF-alpha mutants binding specifically either to the p55 or to the p75 TNF receptors showed that there is a preference of TNF-alpha for the p55 receptor in the mediation of Hp release by neutrophils. A stimulated release of Hp was also induced by the chemotactic tripeptide fMLP. The TNF-alpha-induced release of Hp from neutrophils was inhibited by erbstatin, a tyrosine kinase inhibitor. These findings suggest that TNF-alpha may promptly increase the level of Hp at sites of infection or injury, leading to the modulation of the acute inflammatory response.
触珠蛋白（Hp）、肿瘤坏死因子-α（TNF-α）和中性粒细胞是参与炎症过程的高度相互作用的整体的组成部分。Hp被中性粒细胞摄取，储存在细胞质颗粒区室中，并在这些细胞吞噬作用期间分泌。在本研究中，研究了TNF-α对人中性粒细胞释放Hp的影响。如蛋白质印迹分析和免疫荧光所示，用TNF-α孵育中性粒细胞以时间和浓度依赖性方式诱导细胞释放Hp。TNF-α诱导的Hp释放不是由于细胞的非特异性裂解。TNF-α是一种高度多效性细胞因子，通过与两种不同的受体（p55和p75）结合来介导其作用。给予特异性结合p55或p75 TNF受体的TNF-α突变体表明，在中性粒细胞介导的Hp释放中，TNF-α对p55受体有偏好。趋化性三肽fMLP也诱导了Hp的刺激释放。酪氨酸激酶抑制剂埃布他汀抑制了TNF-α诱导的中性粒细胞释放Hp。这些发现表明，TNF-α可能迅速增加感染或损伤部位的Hp水平，从而导致急性炎症反应的调节。
