SECRETION OF TRANSFORMING GROWTH-FACTOR-ALPHA (TGF-ALPHA) BY POSTNATAL RABBIT ALVEOLAR MACROPHAGES

Transforming growth factor-alpha (TGF alpha) is a cytokine secreted by stimulated alveolar macrophages (AM) in vitro and after in vivo parti culate or hyperoxia exposure and has been implicated in the processes of postnatal lung development. It is unknown if AM TGF alpha secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits on postnatal d 0-2, 5-7, 9-10, 14, 21, and 2 8 and >4 mo (adult), AM were isolated by discontinuous density centrif ugation and placed in culture in the presence or absence of concanaval in A (ConA) for 24 h. Media were collected, and the concentration and isoforms of TGF alpha in AM media samples were determined by an epider mal growth factor/TGF alpha radioreceptor assay and Western immunodete ction, respectively. TGF alpha was present in media of AM from the 1.0 6 and 1.08 g/dL Percoll densities, but not in the 1.10 g/dL density. S tatistically significant differences in TGF alpha: secretion by unstim ulated and ConA-stimulated AM al the various ages were not detected un til d 14 (p < 0.02). Western blot analysis of unstimulated AM media sa mples from d 0-7 rabbits demonstrated the presence of TGF alpha isofor ms at 46, 30, and 14.3 kD. At later postnatal ages (greater than or eq ual to d 9), a single 14.3-kD isoform was present. In contrast, analys is of ConA-stimulated AM media samples showed TGF alpha isoforms at 46 , 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was p resent only in juvenile (d 28) and adult media. These results demonstr ate an age-dependent effect on AM TGF alpha secretion and biochemical isoforms.