Intra-alveolar Release of a Competence-type Growth Factor after Lung Injury1–3

Abstract

Growth factors released by platelets, macrophages, and endothelial and smooth muscle cells have been recognized and characterized using in vitro tests of isolated cell populations. However, their production, secretion, and effects on target cells in situ after tissue injury remains largely presumptive. Alveolar macrophages cultured during acute and chronic lung injury release increased amounts of macrophage-derived growth factor (MDGF). In the present study, we sampled the alveolar lining fluid by lavage for the presence of macromolecular competence factor activity. We report that alveolar lavage fluid obtained following acute lung injury induced by bleomycin in the rat contains large amounts of soluble growth factor activity not found in lung lavage fluid from normal animals. We compared the properties of the growth factor found in fresh lavage fluid to MDGF and platelet-derived growth factor (PDGF). The amount of growth factor in lavage fluid paralleled the ability of cultured alveolar macrophages to release MDGF. Like PDGF and MDGF, lavage fluid growth factor served as a competence factor promoting the reentry of quiescent fibroblasts into the cell cycle rather than as a progression factor. Chromatography on DEAE-Sephacel yielded a single peak of growth factor activity eluting at 0.3 M NaCl. On the basis of these and other physical and biologic properties, we conclude that growth factor activity found in high levels in the alveolar space following acute lung injury resembles MDGF. Growth factor present in the alveolar space may provide the major local stimulus to lung structural cell replication after acute lung injury.