Human Alveolar Macrophage Inhibition of Lung Fibroblast Growth

The processes controlling fibrosis in the human lung are poorly understood. Mononuclear cells may be important regulators of fibroblast function, and the alveolar macrophage (AM) is the major mononuclear phagocyte of the human lung. to further understand AM-fibroblast interactions in the lung, supernatants from unstimulated and stimulated adherent human AM were obtained and their effect on the log phase growth of human lung fibroblasts was characterized. Alveolar macrophage supernatants inhibited fibroblast growth in a dose-dependent fashion. This inhibition was the result of a heat-stable (56° C, 1 h), nondialyzable (molecular weight cutoff, 12,000 daltons), soluble factor(s), which was preferentially elaborated by smaller and denser macrophage subpopulations. The inhibitory capacity of an AM supernatant was directly related to its capacity to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by AM supernatants....