THE CD14 DIFFERENTIATION ANTIGEN MEDIATES THE DEVELOPMENT OF ENDOTOXIN RESPONSIVENESS DURING DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES

The CD14 antigen was originally described as a differentiation antigen on mononuclear cells. The purpose of this study was to investigate th e relationship between the appearance of surface CD14 and the acquisit ion of lipopolysaccharide (LPS) responsiveness during maturation of mo nonuclear phagocytes. Immature THP-1 cells responded poorly to LPS in the absence or presence of serum. Treatment with the maturational agen t calcitriol caused a dose- and time-dependent increase in CD14 mRNA a nd surface CD14 and enhanced the responsiveness of THP-1 cells to smoo th and rough form LPS, complexes of LPS and lipopolysaccharide-binding protein (LBP), and LPS in low concentrations of serum. Monoclonal ant ibodies to CD14 blocked the responses of THP-1 to LPS, LPS-LBP complex es and LPS in serum. Immunodepletion of LBP from serum also inhibited the effect of LPS in serum. The data show that maturation of the respo nse of THP-1, cells to LPS and LPS-LBP complexes depends on the appear ance of CD14 on the cell surface. Maturation of the response to LPS in serum depends in large part on the appearance of CD14 on the cell sur face and the presence of LBP in serum.