Macrophage production of basic fibroblast growth factor in the fibroproliferative disorder of alveolar fibrosis after lung injury.

In organ repair following injury, macrophages accumulate and granulation tissue, comprised of fibroblasts and endothelial cells, develops in the injured area. Basic fibroblast growth factor (bFGF), a potent stimulator of fibroblast and endothelial cell growth, has been linked to the fibroproliferative process. Macrophages are thought to play a central role in the fibroproliferative response, and prior studies indicate that they produce bFGF. Whereas it is plausible that macrophages produce bFGF in a fibroproliferative process, currently no data exists that directly identifies the macrophage as a source of bFGF in a fibroproliferative disorder. We used the model of acute intraalveolar granulation tissue formation following lung injury to determine if the macrophage was a cellular source of bFGF in a naturally occurring fibroproliferative process. To examine this hypothesis, patients with severe acute lung injury underwent bronchoalveolar lavage during the phase of lung repair. Polymerase chain reaction and Northern analysis of macrophage RNA revealed the presence of two species of bFGF messenger RNA (4.4 kb and 1.9 kb). Metabolic labeling studies of recovered macrophages revealed a newly synthesized 18-kd protein with antigenic similarity to bFGF. Immunohistochemical evaluation of lung tissue from patients who died following acute lung injury, showed numerous bFGF immunoreactive macrophages present within airspaces containing fibroblastic and vascular tissue proliferation. This investigation has identified the alveolar macrophage as a cellular source of bFGF in the fibroproliferative disorder of intraalveolar fibrosis following acute lung injury.