Elbim C, Bailly S, Chollet-Martin S, Hakim J, Gougerot-Pocidalo M A
Institut National de la Santé et de la Recherche Médicale U294 et Laboratoire d'Immunologie et d'Hématologie, CHU X. BICHAT, Paris, France.
Infect Immun. 1994 Jun;62(6):2195-201. doi: 10.1128/iai.62.6.2195-2201.1994.
Cytokines such as tumor necrosis factor alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 8 (IL-8), IL-6, IL-1 alpha, and IL-1 beta produced during the immune and inflammatory responses to bacterial stimuli have been reported to interact with polymorphonuclear neutrophil (PMN) activities. However, contradictory findings on their direct and priming effects on the PMN oxidative burst, which is essential for bacterial killing, have been reported. We have used a flow cytometry method to study the effects of these cytokines on the oxidative burst of PMN in whole blood to avoid PMN activation related to isolation procedures. None of the cytokines tested directly activated the PMN oxidative burst, but they did have differential priming effects on the oxidative burst in response to bacterial N-formyl peptides. TNF, GM-CSF, and IL-8 strongly primed a subpopulation of PMN to produce H2O2 in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), while IL-1 alpha, IL-1 beta, and IL-6 failed to do so. Furthermore, the addition of TNF, GM-CSF, or IL-8 to whole blood increased the capacity of a subpopulation of PMN to bind N-formyl peptides, a phenomenon that could account, at least in part, for the strong H2O2 production in response to FMLP after priming by the cytokines. The size of the primed hyperresponsive subpopulation was greater after priming with TNF or GM-CSF than after priming with IL-8. However, GM-CSF, TNF, and IL-8 at suboptimal concentrations cooperated in the induction of a subpopulation hyperresponsive to FMLP. These results show that, of the various proinflammatory cytokines tested, TNF, GM-CSF, and IL-8 strongly prime the PMN oxidative burst in response to bacterial peptides in whole blood and suggest that these cytokines may play a critical role in bacterial killing in vivo.
据报道，在对细菌刺激的免疫和炎症反应过程中产生的细胞因子，如肿瘤坏死因子α（TNF-α）、粒细胞巨噬细胞集落刺激因子（GM-CSF）、白细胞介素8（IL-8）、IL-6、IL-1α和IL-1β，可与多形核中性粒细胞（PMN）的活性相互作用。然而，关于它们对PMN氧化爆发（这对细菌杀伤至关重要）的直接和预激作用，已有相互矛盾的研究结果报道。我们采用流式细胞术方法研究这些细胞因子对全血中PMN氧化爆发的影响，以避免与分离程序相关的PMN激活。所测试的细胞因子均未直接激活PMN氧化爆发，但它们对细菌N-甲酰肽刺激后的氧化爆发具有不同的预激作用。TNF、GM-CSF和IL-8强烈预激PMN亚群，使其在受到N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）刺激时产生H2O2，而IL-1α、IL-1β和IL-6则不能。此外，向全血中添加TNF、GM-CSF或IL-8可增加PMN亚群结合N-甲酰肽的能力，这一现象至少可部分解释细胞因子预激后PMN对FMLP产生强烈H2O2的原因。用TNF或GM-CSF预激后，预激的高反应性亚群的大小比用IL-8预激后的更大。然而，次优浓度的GM-CSF、TNF和IL-8协同诱导了对FMLP高反应的亚群。这些结果表明，在所测试的各种促炎细胞因子中，TNF、GM-CSF和IL-8强烈预激全血中PMN对细菌肽的氧化爆发，并提示这些细胞因子可能在体内细菌杀伤中起关键作用。
