Human alveolar macrophage growth factor for fibroblasts

the alveolar structures is controlled within narrow lim-its by a strictly modulated rate of fibroblast replication. One possible source of growth-modulating signals for alveolar fibroblasts is the alveolar macrophage, a mem-ber of the mononuclear phagocyte family of cells, which collectively are known to be important sources of growth factors for a variety of target cells. To eval-uate the role of alveolar macrophages in the control of alveolar fibroblast replication, macrophages from normal individuals obtained by bronchoalveolar la-vage were maintained in suspension culture with and without added stimuli, and supernates were evaluated for fibroblast growth-promoting effect. Supernates from unstimulated macrophages contained no growth factor activity. In marked contrast, supernates from macrophages stimulated with particulates and im-mune complexes contained a growth factor that caused a significant increase in fibroblast replication rate. Maximum growth factor activity was observed 3-4 h after macrophage stimulation, at a concentration of 1-2 X 106 macrophages/ml. The alveolar macrophage-derived growth factor eluted from DEAE-cellulose at 0.27 M NaCI at neutral pH had an apparent molecular weight of 18,000, and appeared to be distinct from other characterized growth factors. The alveolar mac-rophage-derived growth factor stimulated lung fibro-blast DNA synthesis within 12 h, with cell division apparent within 48 h. In serum-free culture, the al-veolar macrophage-derived growth factor by itself did not promote fibroblast replication, but rather acted as a progression factor causing a synergistic increase in fibroblast replication rate in the presence of compe-tence factors such as fibroblast growth factor or plate-let-derived growth factor. These studies suggest that Received for publication 21 December 1981 and in re-vised form 1I June 1982. when stimulated, human alveolar macrophages may modulate, in part, the replication rate of alveolar fi-broblasts by releasing a growth factor within the al-veolar microenvironment