VARIATION IN THE BIOCHEMICAL-FORMS OF TRANSFORMING GROWTH-FACTOR-ALPHA PRESENT IN HUMAN-MILK AND SECRETED BY HUMAN-MILK MACROPHAGES

Transforming growth factor-alpha (TGF-alpha), present in human milk, i s thought to play a significant role in postnatal gut development. Mac rophages, which abound in human milk, are known to secrete various iso forms of TGF-alpha in other areas of the body. It was hypothesized tha t human milk macrophages (HMM) secrete TGF-alpha, and HMM are a source of TGF-alpha isoforms present in human milk. We sought to measure in vitro HMM TGF-alpha secretion, and to compare the TGF-alpha isoform(s) present in human milk with those secreted by HMM. Study Design: Colos trum and mature milk samples, obtained from mothers (n = 48) on postpa rtum days 3-30, were centrifuged, HMM were isolated, placed in culture for 24 h, and cell-free media collected. The biochemical forms of TGF -alpha in media in human milk supernatant samples were identified by W estern blot analysis under reducing conditions. The concentration of t he mature (6-kD) TGF-alpha isoform in those samples was quantified usi ng a radioimmunoassay, Results: Western blot analysis under reducing c onditions identified a single 6-kD TGF-alpha isoform in all human milk supernatant samples tested, but variable (6- and 30- to 46-kD) TGF-al pha isoforms in HMM media. The mean (+/- SE) concentration of the 6-kD TGF-alpha isoform found in human milk supernatants was 706 +/- 88 pg/ ml and 17.6 +/- 2.6 pg/ml in HMM media. Conclusion: These experiments show that HMM secrete TGF-alpha in biochemical forms both similar to a nd distinct from that found in human milk supernatant.