Ishii Y, Yang H, Sakamoto T, Nomura A, Hasegawa S, Hirata F, Bassett D J
Department of Occupational, Wayne State University, Detroit, Michigan, USA
Toxicol Appl Pharmacol. 1997 Dec;147(2):214-23. doi: 10.1006/taap.1997.8275.
The alveolar macrophage generation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) cytokines has been implicated in the recruitment of neutrophils into acutely injured lungs. To examine the role of these cytokines in neutrophil chemotaxis, cytokine mRNA transcripts and content were examined in macrophages lavaged from rats immediately following 6 hr exposure to air or 1 ppm ozone. Ozone exposure enhanced the number of lavaged macrophages demonstrating mRNA transcripts and immunocytochemical staining for IL-1 beta and TNF-alpha. These changes occurred prior to ozone-induced increases in permeability and lavageable neutrophils. The supernatant from in vitro macrophage cultures demonstrated ozone-associated enhancements in neutrophil chemotactic activity and in IL-1 beta and TNF-alpha levels. However, treatment of the macrophage-conditioned media with anti-IL-1 beta and anti-TNF-alpha antibodies separately and in combination demonstrated that these cytokines were not directly responsible for the observed neutrophil chemoattraction. However, coculturing the macrophages with anti-IL-1 beta and anti-TNF-alpha together, but not separately, resulted in a 44% inhibition of media chemotactic activity, suggesting that maximal macrophage generation of chemoattractants was dependent on either IL-1 beta or TNF-alpha. The mRNA transcripts for the neutrophil chemoattractants macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) were found to be enhanced in cultured macrophages from ozone-exposed rats, but reduced on incubation with anti-IL-1 beta and anti-TNF-alpha together. These results demonstrated that ozone-induced enhancements in IL-1 beta and TNF-alpha productions appear not to be associated directly with neutrophil chemoattraction, but are more likely involved in stimulating the generation of the neutrophil chemoattractants MIP-2 and CINC.
肺泡巨噬细胞产生的白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）细胞因子与中性粒细胞募集到急性损伤肺中有关。为了研究这些细胞因子在中性粒细胞趋化性中的作用，在大鼠暴露于空气6小时或1 ppm臭氧后立即对灌洗出的巨噬细胞中的细胞因子mRNA转录本和含量进行了检测。臭氧暴露增加了显示IL-1β和TNF-α的mRNA转录本及免疫细胞化学染色的灌洗巨噬细胞数量。这些变化发生在臭氧诱导的通透性增加和可灌洗中性粒细胞增加之前。体外巨噬细胞培养物的上清液显示出与臭氧相关的中性粒细胞趋化活性以及IL-1β和TNF-α水平的增强。然而，分别和联合用抗IL-1β和抗TNF-α抗体处理巨噬细胞条件培养基表明，这些细胞因子并非直接导致观察到的中性粒细胞趋化作用。但是，将巨噬细胞与抗IL-1β和抗TNF-α共同培养（而非单独培养）导致培养基趋化活性受到44%的抑制，这表明巨噬细胞产生趋化因子的最大值依赖于IL-1β或TNF-α。发现臭氧暴露大鼠的培养巨噬细胞中中性粒细胞趋化因子巨噬细胞炎性蛋白-2（MIP-2）和细胞因子诱导的中性粒细胞趋化因子（CINC）的mRNA转录本增加，但与抗IL-1β和抗TNF-α一起孵育时减少。这些结果表明，臭氧诱导的IL-1β和TNF-α产生增加似乎与中性粒细胞趋化作用没有直接关联，而更可能参与刺激中性粒细胞趋化因子MIP-2和CINC的产生。
