Warheit D B, George G, Hill L H, Snyderman R, Brody A R
Lab Invest. 1985 May;52(5):505-14.
Pulmonary macrophages migrate to the sites where inhaled chrysotile asbestos fibers initially are deposited (i.e., surfaces of alveolar duct bifurcations). These macrophages have been shown to form a major component of an early asbestos-induced interstitial lesion in rats. In this report, we describe a potential mechanism by which macrophages are attached to these sites of fiber deposition. Chrysotile asbestos fibers used in vitro activate complement proteins in peripheral blood serum and in lavaged cell-free lung proteins. After brief inhalation of chrysotile asbestos, fluids lavaged from the lungs of exposed rats contain substantial chemotactic activity for macrophages compared to fluids from sham-exposed animals (p less than 0.01). We hypothesize that this chemotactic activity is derived from complement activated by inhaled asbestos on alveolar surfaces. This contention is supported by the following observations. Production of chemotactic activity by asbestos in vitro in serum or in lavaged lung fluids was blocked by complement inhibitors. Fractionation, by molecular sieve chromatography, of serum proteins and concentrated proteins lavaged from the lungs of asbestos-exposed rats showed that chemotactic activity was detected in the 14,000- to 18,000-dalton range. This fractionation profile is similar to C5a, the chemotactic product of complement activation. Rats treated with cobra venom factor to deplete circulating complement as well as complement-deficient mice demonstrated significantly depressed macrophage accumulation at sites of asbestos deposition. Pulmonary macrophages are the cells that form the initial inflammatory response to asbestos inhalation. Our findings support the hypothesis that asbestos fibers, and possibly other inhaled particulates, activate complement-derived chemotactic activity on alveolar surfaces. Consequently, macrophages are attracted to the alveolar duct bifurcations where inhaled asbestos fibers are deposited, and this is where the initial lesion of asbestosis is manifested.
肺巨噬细胞迁移至吸入的温石棉纤维最初沉积的部位（即肺泡管分支表面）。这些巨噬细胞已被证明是大鼠早期石棉诱导的间质性病变的主要组成部分。在本报告中，我们描述了巨噬细胞附着于这些纤维沉积部位的一种潜在机制。体外使用的温石棉纤维可激活外周血清和灌洗的无细胞肺蛋白中的补体蛋白。与假暴露动物的灌洗液相比，短暂吸入温石棉后，暴露大鼠肺灌洗液对巨噬细胞具有显著的趋化活性（p小于0.01）。我们假设这种趋化活性源自肺泡表面吸入的石棉激活的补体。以下观察结果支持了这一论点。血清或肺灌洗液中石棉体外产生的趋化活性被补体抑制剂阻断。通过分子筛色谱法对石棉暴露大鼠肺灌洗的血清蛋白和浓缩蛋白进行分级分离表明，趋化活性在14,000至18,000道尔顿范围内被检测到。这种分级分离谱与补体激活的趋化产物C5a相似。用眼镜蛇毒因子处理以耗尽循环补体的大鼠以及补体缺陷小鼠在石棉沉积部位的巨噬细胞积累明显减少。肺巨噬细胞是对吸入石棉形成初始炎症反应的细胞。我们的研究结果支持以下假设：石棉纤维以及可能的其他吸入颗粒物在肺泡表面激活补体衍生的趋化活性。因此，巨噬细胞被吸引到吸入石棉纤维沉积的肺泡管分支处，而这正是石棉沉着病初始病变的表现部位。
