König B, König W
Medizinische Mikrobiologie und Immunologie, AG Infektabwehr, Ruhr-Universität Bochum, Germany.
Infect Immun. 1994 May;62(5):2085-93. doi: 10.1128/iai.62.5.2085-2093.1994.
Previously, we have shown that Escherichia coli alpha-hemolysin represents a potent stimulus for inflammatory mediator release (O2- release, beta-glucuronidase release, and leukotriene generation) from human polymorphonuclear granulocytes (PMN) as well as for histamine release from a human lymphocyte-monocyte-basophil cell suspension (LMB). In contrast, the E. coli alpha-hemolysin leads to a downregulation of cytokine release (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-1 beta) from human LMB. This study was undertaken (i) to analyze the priming efficacy of growth factors (granulocyte-macrophage colony-stimulating factor [GM-CSF] and granulocyte CSF [G-CSF]) on inflammatory mediator release from human PMN and LMB challenged with hemolysin-producing E. coli bacteria as well as with cell-free E. coli alpha-hemolysin and (ii) to identify major components involved in GM-CSF and G-CSF priming. GM-CSF pretreatment led to an increased chemiluminescence response from human PMN by up to 100%, leukotriene B4 generation was enhanced up to fivefold, and histamine release from human LMB increased from 45% +/- 15% to 75% +/- 5% (mean +/- standard distribution) of the total histamine content. G-CSF priming induced an increase in the chemiluminescence response by up to 50% +/- 5% from human PMN and an increase in histamine release from human LMB by 20% +/- 5%. The growth factors, GM-CSF and G-CSF, modulated neither beta-glucuronidase release from human PMN nor IL-8 release from human PMN and LMB challenged with the E. coli alpha-hemolysin. GM-CSF and G-CSF pretreatment increased the fluoride (NaF)-induced chemiluminescence response by up to 10-fold; the serine/threonine phosphatase inhibitor okadaic acid inhibited GM-CSF- and G-CSF-induced priming. NaF-induced histamine release was enhanced up to 60 and 30% by GM-CSF and G-CSF priming, respectively. GM-CSF and G-CSF pretreatment did not modulate phorbol 12-myristate 13-acetate-induced chemiluminescence response or histamine release. GM-CSF by itself induced an increase in 5-lipoxygenase-specific mRNA expression within 5 min. Our results indicate that (i) GM-CSF and G-CSF interact with inflammatory cells via distinct cellular signalling, (ii) the signal transduction pathway is dependent on the cellular mediator, and (iii) the use of growth factors may be a potent tool to influence the clinical outcome in infectious diseases.
此前，我们已经表明，大肠杆菌α-溶血素是人类多形核粒细胞（PMN）释放炎症介质（超氧阴离子释放、β-葡萄糖醛酸酶释放和白三烯生成）以及人类淋巴细胞-单核细胞-嗜碱性粒细胞悬液（LMB）释放组胺的有力刺激物。相比之下，大肠杆菌α-溶血素会导致人类LMB细胞因子释放（白细胞介素6 [IL-6]、肿瘤坏死因子α和IL-1β）下调。本研究旨在：（i）分析生长因子（粒细胞-巨噬细胞集落刺激因子[GM-CSF]和粒细胞集落刺激因子[G-CSF]）对受产溶血素大肠杆菌以及无细胞大肠杆菌α-溶血素刺激的人类PMN和LMB释放炎症介质的启动作用；（ii）确定参与GM-CSF和G-CSF启动的主要成分。GM-CSF预处理使人类PMN的化学发光反应增加高达100%，白三烯B4生成增加高达五倍，人类LMB的组胺释放从总组胺含量的45%±15%增加到75%±5%（平均值±标准差）。G-CSF启动使人类PMN的化学发光反应增加高达50%±5%，使人类LMB的组胺释放增加20%±5%。生长因子GM-CSF和G-CSF对受大肠杆菌α-溶血素刺激的人类PMN的β-葡萄糖醛酸酶释放以及人类PMN和LMB的IL-8释放均无调节作用。GM-CSF和G-CSF预处理使氟化物（NaF）诱导的化学发光反应增加高达10倍；丝氨酸/苏氨酸磷酸酶抑制剂冈田酸可抑制GM-CSF和G-CSF诱导的启动。GM-CSF和G-CSF启动分别使NaF诱导的组胺释放增加高达60%和30%。GM-CSF和G-CSF预处理未调节佛波酯12-肉豆蔻酸酯13-乙酸酯诱导的化学发光反应或组胺释放。GM-CSF自身在5分钟内可诱导5-脂氧合酶特异性mRNA表达增加。我们的结果表明：（i）GM-CSF和G-CSF通过不同的细胞信号传导与炎症细胞相互作用；（ii）信号转导途径取决于细胞介质；（iii）生长因子的使用可能是影响传染病临床结果的有力工具。
