Lymphokine regulation of macrophage-derived growth factor secretion following pulmonary injury

Abstract

Rat alveolar macrophages secrete enhanced levels of a growth factor for fibroblasts following acute lung injury. The authors have previously identified this anionic, heat-labile substance as macrophage-derived growth factor (MDGF) and have now focused on how its release by alveolar macrophages is controlled following lung damage. In response to pulmonary injury induced with a single intratracheal instillation of bleomycin sulfate, the lymphocyte count rose from undetectable to 23% of the cells retrieved in lavage fluid. Spontaneous MDGF secretion by macrophages cultured from the same lungs generally paralleled the changes in lymphocyte counts over time. To test whether lymphokine(s) secreted by alveolar lymphocytes regulated MDGF secretion by macrophages in this model, the authors exposed normal macrophages harvested from control rat lungs to lymphokine preparations in vitro. Lymphokines provided a powerful stimulus to normal macrophages, inducing MDGF secretion at dilutions as low as 10(-6). Fractionating T-lymphocyte subsets by adherence to monoclonal antibodies indicated that the W3/25+ cells elaborated the macrophage-stimulating lymphokine, but that OX8+ cells did not. Furthermore, recombinant murine gamma interferon was capable of substituting for native lymphokine in activating MDGF secretion by normal macrophages. It is concluded that immune stimulation of fibroblast proliferation requires cooperative interaction of both lymphocytes and macrophages in this model of acute lung injury.