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 granulati on tissue, comprised of fibroblasts and endothelial cells, develops in the injured area. Basic fibroblast growth factor (bFGF), a potent sti mulator of fibroblast and endothelial cell growth, has been linked to the fibroproliferative process. Macrophages are thought to play a cent ral role in the fibroproliferative response, and prior studies indicat e that they produce bFGF. Whereas it is plausible that macrophages pro duce bFGF in a fibroproliferative process, currently xo data exists th at directly identifies the macrophage as a source of bFGF in a fibropr oliferative disorder. We used the model of acute intraalveolar granula tion tissue formation following lung injury to determine if the macrop hage was a cellular source of bFGF in a naturally occurring fibroproli ferative process To examine this hypothesis, patients with severe acut e lung injury underwent bronchoalveolar lavage during the phase of lun g repair. Polymerase chain reaction and Northern analysis of macrophag e RNA revealed the presence of two species of bFGF messenger RNA (4.4 kb and 1.9 kb). Metabolic labeling studies of recovered macrophages re vealed a newly synthesized 18-kb 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 vascu lar tissue proliferation. This investigation has identified the alveol ar macrophage as a cellular source of bFGF in the fibroproliferative d isorder of intraalveolar fibrosis following acute lung injury.