Secretion of transforming growth factor-α (TGFα) by postnatal rabbit alveolar macrophages

Abstract

Transforming growth factor-α (TGF α) is a cytokine secretec by stimulated alveolar macrophages (AM) in vitro and after it vivo particulate or hyperoxia exposure and has been implicated ir the processes of postnatal lung development. It is unknown if AM TGFα secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits or postnatal d 0-2, 5-7, 9-10, 14, 21, and 28 and >4 mo (adult) AM were isolated by discontinuous density centrifugation anc placed in culture in the presence or absence of concanavalin A (ConA) for 24 h. Media were collected, and the concentratior and isoforms of TGFα in AM media samples were determined b) an epidermal growth factor/TGFα radioreceptor assay and Western immunodetection, respectively. TGFα was present in medi; of AM from the 1.06 and 1.08 g/dL Percoll densities, but not ir the 1.10 g/dL density. Statistically significant differences ir TGFα secretion by unstimulated and ConA-stimulated AM at the various ages were not detected until d 14 (p < 0.02). Westerr blot analysis of unstimulated AM media samples from d 0-7 rabbits demonstrated the presence of TGFα isoforms at 46, 30, and 14.3 kD. At later postnatal ages (> d 9), a single 14.3-kD isoform was present. In contrast, analysis of ConA-stimulated AM media samples showed TGFα isoforms at 46, 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was present only in juvenile (d 28) and adult media. These results demonstrate an age-dependent effect on AM TGF α secretion and biochemical isoforms. © 1995 International Pediatric Research Foundation, Inc.