Strieter R M, Kasahara K, Allen R M, Standiford T J, Rolfe M W, Becker F S, Chensue S W, Kunkel S L
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Am J Pathol. 1992 Aug;141(2):397-407.
During acute inflammation, the first line of cellular response for host defense is the neutrophil. In addition to the historic role of the neutrophil as a phagocyte, recent studies have identified this cell as an important source of a number of cytokines. In this study, we provide evidence that the neutrophil is a significant source of interleukin-8 (IL-8). Neutrophils freshly isolated from whole blood were not found to constitutively express IL-8 mRNA. In contrast, when these leukocytes were cultured on plastic they were activated, leading to the significant expression of de novo steady-state levels of IL-8 mRNA. In addition, when neutrophils were treated with cycloheximide, there was evidence for "superinduction" of steady-state levels of IL-8 mRNA and inhibition of antigenic IL-8 production. Neutrophils were subsequently stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha, or interleukin-1-beta and were found to express IL-8 mRNA and antigen in both a time- and dose-dependent manner. Furthermore, neutrophils stimulated with traditional chemotactic/activating factors, such as the split product of the fifth component of complement (C5a), formylmethionyleucylphenylalanine (fMLP), and leukotriene B4 (LTB4) in a dose-dependent manner did not produce significant antigenic IL-8, as compared with unstimulated controls. In contrast, when neutrophils were exposed to either of these neutrophil agonists in the presence of LPS, the production of antigenic IL-8 was significantly elevated, as compared with either of the stimuli alone, suggesting a synergistic response. These data would suggest that the neutrophil can no longer be viewed as only a phagocyte or warehouse for proteolytic enzymes, but is a pivotal effector cell that is able to respond to mediators in its environment and generate cytokines. This latter neutrophil response may be important for either the elicitation of additional neutrophils or to orchestrate the conventional immune response at sites of inflammation.
在急性炎症期间，宿主防御的细胞反应的第一线是中性粒细胞。除了中性粒细胞作为吞噬细胞的传统作用外，最近的研究已将这种细胞鉴定为多种细胞因子的重要来源。在本研究中，我们提供证据表明中性粒细胞是白细胞介素-8（IL-8）的重要来源。从全血中新鲜分离的中性粒细胞未发现组成性表达IL-8 mRNA。相反，当这些白细胞在塑料上培养时，它们被激活，导致从头合成的IL-8 mRNA稳态水平显著表达。此外，当中性粒细胞用放线菌酮处理时，有证据表明IL-8 mRNA稳态水平的“超诱导”和抗原性IL-8产生的抑制。随后用脂多糖（LPS）、肿瘤坏死因子-α或白细胞介素-1-β刺激中性粒细胞，发现它们以时间和剂量依赖的方式表达IL-8 mRNA和抗原。此外，与未刺激的对照相比，用传统趋化/激活因子如补体第五成分（C5a）的裂解产物、甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）和白三烯B4（LTB4）以剂量依赖的方式刺激中性粒细胞不会产生显著的抗原性IL-8。相反，当中性粒细胞在LPS存在下暴露于这些中性粒细胞激动剂中的任何一种时，与单独的任何一种刺激相比，抗原性IL-8的产生显著升高，表明存在协同反应。这些数据表明，中性粒细胞不能再仅仅被视为吞噬细胞或蛋白水解酶的储存库，而是一个关键的效应细胞，能够对其环境中的介质作出反应并产生细胞因子。中性粒细胞的后一种反应对于引发更多中性粒细胞或协调炎症部位的传统免疫反应可能很重要。
