Secretion of Macrophage-Derived Growth Factor During Acute Lung Injury Induced by Bleomycin

Abstract

Monocytes are capable of producing a growth factor which causes fibroblasts to replicate in vitro. This macrophage-derived growth factor (MDGF) may be particularly important in controlling the proliferation of mesenchymal cells in the pulmonary interstitium following acute lung injury. To evaluate the role of macrophages in modulating the proliferative capacity of fibroblasts, we added serum-free culture medium from lavage-derived rat lung macrophages to confluent monolayers of quiescent adult rat lung fibroblasts and monitored their return to the cell cycle both by ³H-thymidine incorporation and by increases in cell number. Growth factor activity secreted in 24 h by untreated macrophages was compared to that from normal macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) and from macrophages retrieved from lungs injured by intratracheal administration of bleomycin. Unstimulated macrophages from control animals secreted minimal amounts of MDGF; addition of LPS to normal macrophages increased MDGF secretion 3- to 4-fold. Adherent cells obtained by lung lavage of bleomycin-treated animals spontaneously secreted near maximal levels of nondialyzable MDGF with little further stimulation by LPS. The MDGF secreted by LPS-stimulated control cells and by macrophages retrieved from injured lungs share identical elution profiles from DEAE-Sepha- cel anionic exchange columns, and heat stability profiles. The substance acts as a competence factor when tested on rat lung fibroblasts. These shared physical and biologic properties suggest that the growth factor secreted by cells lavaged from injured lungs is identical to MDGF secreted in response to LPS. Because MDGF release could not be induced by direct exposure of freshly isolated macrophages to bleomycin, we suggest that augmented release of MDGF is an indirect feature of acute lung injury in this model.