Asbestos exposure stimulates pleural mesothelial cells to secrete the fibroblast chemoattractant, fibronectin

Parietal pleural plaques and visceral pleural fibrosis are well-recognized stigmata of occupational asbestos exposure. However, their pathogenesis is poorly understood. Conceivably, phagocytosis of asbestos fibers by pleural mesothelial cells may stimulate the recruitment of fibroblasts to sites of asbestos-induced pleural injury. To test this hypothesis, rat parietal pleural mesothelial cells were cultured for 6 to 96 h with or without crocidolite or chrysotile asbestos fibers (concentration range, 2 to 100 micrograms/cm2). Asbestos fibers were actively phagocytosed by pleural mesothelial cells and were incorporated within phagosomes. Conditioned medium was assayed for chemotactic activity toward RL-87 rat lung fibroblasts and for fibronectin immunoreactivity. The effects of asbestos were compared with those of alpha-cristobalite (which is strongly fibrogenic), alpha-quartz (a less fibrogenic particulate), and carbonyl iron (a nonfibrogenic agent). Both types of asbestos stimulated the secretion of fibroblast chemoattractant activity by pleural mesothelial cells in a time-dependent manner. This effect peaked at 96 h in cultures containing 4 micrograms/cm2 of asbestos (P < 0.001). alpha-Cristobalite also enhanced the secretion of the mesothelial cell-derived chemoattractant, an effect that was maximal at a concentration of 20 micrograms/cm2 (P < 0.001). Furthermore, crocidolite, chrysotile, and alpha-cristobalite stimulated pleural mesothelial cell fibronectin synthesis. In contrast, alpha-quartz and carbonyl iron particles had no noticeable effect on either immunoreactive fibronectin secretion or chemoattractant release by pleural mesothelial cells. The ability of asbestos fibers and alpha-cristobalite particles to stimulate the secretion of the fibroblast chemoattractant, fibronectin, by pleural mesothelial cells may have relevance to the induction of pleural injury by fibrogenic particulates.