Ouellet S, Yang H, Aubin R A, Hawley R G, Wenckebach G F, Lemaire I
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa, Canada.
J Leukoc Biol. 1993 Mar;53(3):279-86. doi: 10.1002/jlb.53.3.279.
Bronchoalveolar lavage (BAL) cells were isolated from rats 1, 3, and 6 weeks after a single intratracheal instillation of saline, UICC chrysotile asbestos (5 mg), or silica (5 mg). In asbestos-exposed rats, the pulmonary response was characterized by a significant increase in the number of alveolar macrophages (AMs) and the appearance of fibrotic lesions within 1 week. By contrast, mixed macrophage and neutrophil accumulations were observed in the silica group without evidence of fibrosis. Tumor necrosis factor-alpha (TNF-alpha) production by lipopolysaccharide (LPS)-stimulated BAL cells from asbestos-treated rats was significantly lower than controls 1 and 3 weeks after exposure. However, by 6 weeks higher levels of TNF-alpha production were noticeable in this group. Decreases in LPS-induced TNF-alpha production were also observed with BAL cells from silica-treated animals at all time points studied. Lower levels of TNF-alpha were not related to decreased BAL cell viability or the presence of a significant proportion of neutrophils in the silica group. Furthermore, biphasic changes in TNF-alpha production seen in the asbestos group were correlated with concomitant decreases (3 weeks) and increases (6 weeks) in levels of TNF-alpha mRNA in AMs. These data indicate that lower levels of TNF-alpha resulted from inhibition at the gene expression level and provide evidence for bidirectional modulation of TNF-alpha production by AMs during inflammatory reactions.
在大鼠经气管内单次滴注生理盐水、UICC温石棉（5毫克）或二氧化硅（5毫克）后1、3和6周，分离支气管肺泡灌洗（BAL）细胞。在接触石棉的大鼠中，肺部反应的特征是肺泡巨噬细胞（AM）数量显著增加，且在1周内出现纤维化病变。相比之下，在二氧化硅组中观察到混合的巨噬细胞和中性粒细胞积聚，但无纤维化证据。在接触石棉的大鼠中，脂多糖（LPS）刺激的BAL细胞产生的肿瘤坏死因子-α（TNF-α）在接触后1周和3周显著低于对照组。然而，到6周时，该组中TNF-α的产生水平明显更高。在所有研究的时间点，用二氧化硅处理的动物的BAL细胞也观察到LPS诱导的TNF-α产生减少。较低水平的TNF-α与二氧化硅组中BAL细胞活力降低或大量中性粒细胞的存在无关。此外，石棉组中观察到的TNF-α产生的双相变化与AMs中TNF-α mRNA水平的相应降低（3周）和升高（6周）相关。这些数据表明，较低水平的TNF-α是由基因表达水平的抑制导致的，并为AMs在炎症反应期间对TNF-α产生的双向调节提供了证据。
