TRANSFORMING GROWTH-FACTOR-BETA-1 AUGMENTS MACROPHAGE-COLONY-STIMULATING FACTOR ACTIVITY ON HUMAN MARROW

Transforming growth factor-beta 1 (TGF-beta 1) suppresses the colony s timulating activity of most cytokines. The effect of TGF-beta 1 on mac rophage colonies induced by macrophage colony stimulating factor (M-CS F) from human marrow has not been described. Experiments were performe d with phenylalanine methyl ester (PME) treated marrow. PME (5 mM) eli minates stromal cells and monocytes. Colony stimulatory factors were u sed at plateau concentrations. TGF-beta 1 (0.1 ng/ml) significantly (p < 0.05) augmented M CSF induced macrophage colony forming units (CFU- M) by twofold to fourfold in 818 donors. In contrast, colonies stimula ted by granulocyte-macrophage CSF (GM-CSF) (CFU-GM), were significantl y decreased by TGF-beta 1. To determine if TGF-beta 1 was present in e ffective concentrations in vitro, cultures were performed with anti-TG F-beta 1. Anti-TGF-beta 1 decreased (p < 0.05) M-CSF induced colonies in 5/6 donors. The method of TGF-beta 1 enhancement was explored with antihuman CSF-1 receptor antibody. Antihuman CSF-1 receptor antibody r esulted in comparable suppression of CFU-M resulting from both M-CSF a nd M-CSF + TGF-beta 1. These studies indicate that TGF-beta 1 directly enhances M-CSF activity by a mechanism other than upregulation of M-C SF receptors.