Plasma membrane-derived vesicles (PMVs) carry TGF-β and promote adhesion and differentiation of THP-1 monocytes to macrophages (35.15)

Abstract

Abstract Microvesiculation is a ubiquitous cellular mechanism, which occurs as a result of exocytosis, to release exosomes (between 50-100nm) or by direct release of vesicles from the cell surface membrane, known as plasma membrane-derived vesicles (PMVs) (0.1-1μm). Plasma membrane-derived vesicles are small, intact membrane vesicles, which are released by most cells upon activation with various extracellular stimuli and contain numerous proteins and lipids characteristic of the cell of origin. Among these are cytokines, for example transforming growth factor-β (TGF-β), a multifunctional protein, well documented to function in the regulation of cell proliferation, differentiation, morphogenesis and phenotype expression. Since TGF-β plays an important role in cell regulation, we tested whether TGF-β-bearing PMVs derived from THP-1 cells could themselves regulate the growth and differentiation of monocytes and their leukaemic counterparts. We show that addition of PMVs to monocytes or THP-1 cells did indeed cause significant reductions in the growth rate and induced their terminal differentiation into macrophages. Further investigations also showed that PMVs isolated from cells with high TGF-β content, caused significantly higher reductions in the growth rate of THP-1 cells as compared to PMVs from cells, which express less TGF-β. These results present a possible autocrine-like mechanism involving monocyte-derived PMVs by which monocytes terminally differentiate into macrophages.