Inhaled asbestos activates a complement-dependent chemoattractant for macrophages

Abstract

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.