Continuous secretion of monocyte chemotactic factors and fibroblast growth factors by alveolar macrophages following a single exposure to bleomycin in vitro

Abstract

It has been shown in previous studies that alveolar macrophages incubated with bleomycin in vitro for 2 to 18 hours secrete monocyte chemotactic factors and fibroblast growth factors (MDGF). The purpose of the current experiments was to determine if alveolar macrophages similarly stimulated with bleomycin would continue to secrete these factors once the stimulus was removed. Alveolar macrophages from normal rats were exposed to bleomycin for 18 hours after which bleomycin was removed and macrophages maintained in culture for 35 days. Conditioned medium (CM) was collected and assayed at weekly intervals. In comparison with nonstimulated controls, bleomycin-stimulated macrophages secreted greater amounts of both monocyte chemotactic factors and MDGF for 35 days after exposure to bleomycin; with a significant difference noted between bleomycin and control macrophages for the first 21 days (P less than 0.02). In agreement with past work, the chemotactic activity in bleomycin-CM was due to fibronectin, as evidenced by the almost complete inhibition of activity by anti-fibronectin antibodies. The time course of secretion of chemotactic and growth factors after a single exposure to bleomycin in vitro was similar to that induced by in vivo exposure of macrophages to this drug. The data suggest that a similar direct activation of macrophages by bleomycin may promote the long-term production of these factors in vivo, resulting in continued monocyte recruitment and promotion of fibroblast proliferation in fibrotic lungs.