TRANSFORMING GROWTH-FACTOR-BETA MODULATES C3 AND FACTOR-B BIOSYNTHESIS AND COMPLEMENT RECEPTOR-3 EXPRESSION IN CULTURED HUMAN MONOCYTES

Complement biosynthesis in monocytes is stimulated by different pathog ens and modulated by a variety of cytokines, but little is known about the possible effect of transforming growth factor beta (TGF-beta) on this monocyte function. We therefore studied the effect of TGF-beta 1 and TGF-beta 2 on constitutive, lipopolysaccharide (LPS)- and Candida albicans-induced monocyte biosynthesis of complement components C3 and factor B. Under all three conditions, both forms of TGF-beta (20 ng/m l) induced a two- to fourfold increase in C3 concentration in monocyte supernatants harvested after 2 or 5 days of cell culture, an effect t hat was abrogated by cycloheximide. In contrast, constitutive and path ogen-induced production of factor B was suppressed by TGF-beta. The ef fects of TGF-beta on complement production were neutralized by a monoc lonal anti-TGF-beta antibody. Moreover, TGF-beta suppressed the pathog en-induced release of granulocyte-macrophage colony-stimulating factor and down-regulated the expression of complement receptor 3 (CD11b/CD1 8), while the expression of CD11a/CD18, a related beta(2) integrin, wa s unaffected. These novel effects of TGF-beta emphasize the immunomodu latory significance of this cytokine.