We have shown that pulmonary macrophages migrate to the sites where inhaled chrysotile fibers initially are deposited (i.e., surfaces of alveolar duct bifurcations). These macrophages form a major component of an early asbestos-induced interstitial lesion in rats. To establish the basic cellular mechanisms of asbestos-induced lung disease, it is essential to determine the chemical mediators which attract macrophages 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. Fluids lavaged from the lungs of exposed rats contain substantial chemotactic activity for macrophages compared to fluids from sham-exposed animals (p less than .01). We hypothesize that this chemotactic activity is derived from complement activated by inhaled asbestos on alveolar surfaces. This contention is supported by observing that: Production in vitro of chemotactic activity by asbestos in serum or in lung lavageates was blocked by complement inhibitors and that 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 14-18,000 MW range. This fractionation profile is similar to C5a, the chemotactic product of complement activation. In adddition, rats treated with cobra venom factor (CVF) to deplete circulating complement as well as complement-deficient mice demonstrated significantly depressed macrophage accumulation at sites of asbestos deposition. Recently we have learned that the complement-dependent chemotactic factor is activated during a 3-hr exposure to asbestos, peak activity is maintained through 48 hrs post-exposure, but the chemotactic activity is not detectable by 8 days after exposure. Interestingly enough, when CVF-treated rats were exposed to asbestos, their macrophage response returned when circulating complement reached normal levels.
