Zhou J, Zhou L, Yang J
Department of Occupational Health, Suzhou Medical College.
Zhonghua Yu Fang Yi Xue Za Zhi. 1998 Nov;32(6):336-9.
To understand the role of cytokine released from alveolar macrophage (AM) in lung fibrosis caused by mineral dust.
Rabbit's AM obtained by lavage was cultured with mineral dust in vitro. Activities of tumor necrosis factor (TNF) and interleukin 6 (IL-6) in its supernatant were determined with isotope labelling method and MTT colorimetry, respectively. Human fetal lung fibroblast WI-138 was cultured with this supernatant. Proliferation of fibroblast and synthesis of collagen were examined by 3H-thymidine (3H-TdR) and 14C-proline (14C-Pro) incorporation and its total hydroxyproline (HOP) level was analyzed by chloramine-T method.
Proliferation of lung fibroblast and synthesis of collagen could be enhanced by the supernatant containing AM induced by quartz, asbestos and uranium mineral dust, with 3H-TdR incorporated counts per minute (cpm) of 6,584, 3,848 and 6,893 in the group of 100 micrograms 3H-TdR and 14C-Pro incorporated 27,952, 13,416 and 18,538 in the group of 200 micrograms respectively, which were significantly higher than those in the control group. Total HOP levels in the culture media for lung fibroblast enhanced by AM supernatant were 22.41, 24.00 and 21.39 micrograms/ml, respectively, and was significantly higher than that in the control group (12.91 micrograms/ml). Release of TNF and IL-6 could be stimulated by mineral dust, such as quartz, asbestos and uranium mineral dust, and their activities were significantly higher than those in the control group, with those of 1,396, 1,198 and 852 U/ml in TNF group and 1,336, 1511 and 1,335 U/ml in IL-6 group, respectively. Proliferation of lung fibroblast and synthesis of collagen could be inhibited by antibody against TNF and interferon-r (gamma), and the effect of the latter was weaker than that of the former on inhibition of fibroblast proliferation and the effect on collagen synthesis was just in the opposite direction.
Lung fibrosis caused by mineral dust correlated with abnormal expression of TNF and IL-6. Antibody against TNF and gamma interferon could antagonize the effect of NTF and IL-6.
了解肺泡巨噬细胞（AM）释放的细胞因子在矿物粉尘所致肺纤维化中的作用。
通过灌洗获取兔的AM，在体外与矿物粉尘共同培养。分别采用同位素标记法和MTT比色法测定其上清液中肿瘤坏死因子（TNF）和白细胞介素6（IL-6）的活性。将人胚肺成纤维细胞WI-138与该上清液共同培养。通过3H-胸腺嘧啶核苷（3H-TdR）掺入法和14C-脯氨酸（14C-Pro）掺入法检测成纤维细胞的增殖及胶原蛋白的合成，并采用氯胺-T法分析其总羟脯氨酸（HOP）水平。
石英、石棉和铀矿粉尘诱导的含AM的上清液可增强肺成纤维细胞的增殖及胶原蛋白的合成，在100微克3H-TdR组中，3H-TdR每分钟掺入计数（cpm）分别为6584、3848和6893，在200微克14C-Pro组中，14C-Pro掺入量分别为27952、13416和18538，均显著高于对照组。AM上清液增强的肺成纤维细胞培养基中的总HOP水平分别为22.41、24.00和21.39微克/毫升，显著高于对照组（12.91微克/毫升）。矿物粉尘如石英、石棉和铀矿粉尘可刺激TNF和IL-6的释放，其活性显著高于对照组，TNF组分别为1396、1198和852 U/毫升，IL-6组分别为1336、1511和1335 U/毫升。抗TNF抗体和干扰素-γ（γ）可抑制肺成纤维细胞的增殖及胶原蛋白的合成，后者对成纤维细胞增殖的抑制作用弱于前者，对胶原蛋白合成的作用则相反。
矿物粉尘所致肺纤维化与TNF和IL-6的异常表达相关。抗TNF抗体和γ干扰素可拮抗NTF和IL-6的作用。
