title: Modulation of the effects of alveolar macrophages on lung fibroblast collagen production rate.
abstract: Alveolar macrophages (AM) may function as effector cells that can either stimulate or inhibit lung fibroblast collagen production. However, conditions that determine the predominant effect of AM on fibroblasts are not well understood. To delineate factors that modulate the effects of AM on lung fibroblasts, we studied the interaction of AM products and fibroblasts in vitro. The AM were obtained by bronchoalveolar lavage of hamsters with bleomycin-induced pulmonary fibrosis. Conditioned medium (CM) from the AM cultures was incubated in varying amounts with lung fibroblast (IMR-90) cultures. After metabolic labeling with [3H]proline, fibroblast collagen production based on procollagen-specific radioactivity was determined (Anal Biochem 1984; 140:478). Macrophage CM in concentrations greater than 5% suppressed collagen production, an event attributed to the macrophage-derived suppressive factor that we have previously characterized (J Clin Invest 1983; 72:2082). Macrophages were also determined to produce PGE2 in culture (500 pg/10(6) cells). Authentic PGE2 at concentrations found in CM was found to suppress fibroblast collagen production, indicating that AM-derived PGE2 contributes to the suppressive activity in CM. To examine possible stimulatory factors in CM, the fibroblasts were preincubated with indomethacin. This approach was based on our previous observation that AM-derived suppressive factor increases endogenous fibroblast PGE2 and that its activity can be blocked by indomethacin. Macrophage CM in a concentration of 20% did not suppress the collagen production of indomethacin-treated fibroblasts. However, CM concentrations of 5 and 10% increased collagen production (173 and 143% of control values, respectively), indicating the presence of stimulatory factor(s) in macrophage-conditioned medium.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001761:Bleomycin; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D006224:Cricetinae; D015232:Dinoprostone; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008647:Mesocricetus; D011392:Proline / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism; D014316:Tritium
chemical_list: D011458:Prostaglandins E; D014316:Tritium; D001761:Bleomycin; D003094:Collagen; D011392:Proline; D015232:Dinoprostone; D006909:Hydroxyproline; D007213:Indomethacin