Inhibition of lung fibroblast growth by human lung mononuclear cells

Abstract

Mononuclear cell-fibroblast interactions in the normal human lung are poorly understood. To investigate these interactions, we characterized the effect on lung fibroblast growth of supernatants from nonadherent lung mononuclear cells cultured with or without phytohemagglutinin (PHA). Supernatants from unstimulated cells had no effect on fibroblast growth. Supernatants from lung mononuclear cells stimulated by PHA inhibited fibroblast growth in a dose-dependent fashion. This inhibition was mediated by a nondialyzable, noncytotoxic, soluble factor(s) that was partially heat labile and sensitive to digestion with trypsin. Production of this factor(s) was dependent on T-lymphocytes and occurred within 4 h of the initiation of lung mononuclear cell-PHA cultures. Because prostaglandins can mediate mononuclear cell effects on fibroblast growth, we examined the relationship between the inhibition of fibroblast growth caused by PHA-stimulated nonadherent lung mononuclear cells and lung fibroblast prostaglandin production. The nonadherent lung mononuclear cell supernatants stimulated fibroblast PGE2 production, and exogenous PGE2 was capable of inhibiting fibroblast growth. However, the inhibition of fibroblast growth caused by nonadherent lung mononuclear cells stimulated by PHA was not mediated by fibroblast prostaglandin production. Inhibition of lung fibroblast growth by stimulated lung mononuclear cells may be important in regulating fibrosis in the human lung.