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.