Transforming growth factor-beta 1 augments macrophage-colony stimulating factor activity on human marrow.

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) suppresses the colony stimulating activity of most cytokines. The effect of TGF-beta 1 on macrophage colonies induced by macrophage colony stimulating factor (M-CSF) from human marrow has not been described. Experiments were performed with phenylalanine methyl ester (PME) treated marrow. PME (5 mM) eliminates stromal cells and monocytes. Colony stimulatory factors were used 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 8/8 donors. In contrast, colonies stimulated by granulocyte-macrophage CSF (GM-CSF) (CFU-GM), were significantly decreased by TGF-beta 1. To determine if TGF-beta 1 was present in effective concentrations in vitro, cultures were performed with anti-TGF-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 resulted in comparable suppression of CFU-M resulting from both M-CSF and 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-CSF receptors.