HUMAN MONOCYTES AND NEUTROPHILS STORE TRANSFORMING GROWTH-FACTOR-ALPHA IN A SUBPOPULATION OF CYTOPLASMIC GRANULES

Transforming growth factor-alpha (TGF-alpha) exerts several effects on target cells, such as neovascularization promotion and mitogenic sign alling, Using immunoelectron microscopy, we show that monocytes and ne utrophils, store TGF-alpha in cytoplasmic granules. In monocytes, TGF- alpha did not colocalize with components of peroxidase-positive granul es or with albumin of secretory vesicles, Furthermore, no colocalizati on of TGF-alpha with components of azurophilic or specific granules or secretory vesicles was observed in neutrophils, Activated monocytes a nd tissue-macrophages contained much less TGF-alpha-positive granules, suggesting TGF-alpha release. Western blot analysis showed a protein of 10 kD in lysates of monocytes. TGF-alpha mRNA was detected in monoc ytoid cells from the bone marrow by in situ hybridization. This study shows for the first time that monocytes and neutrophils contain TGF-al pha in all stages of maturation and that TGF-alpha in monocytes is sto red in a large population of peroxidase-negative granules suggesting a function for these granules. Monocytes and neutrophils are important effector cells in inflammatory reactions. The present finding that the se cells contain TGF-alpha might explain complications such as fibrosi s and neoplastic transformation, caused by chronic inflammation. (C) 1 997 by The American Society of Hematology.