Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Human macrophages respond to LPS in a serum independent, CD14 dependent manner

Abstract

Two crucial mediators of monocyte activation by lipopolysaccharide (LPS) are the acute phase plasma factor, lipopolysaccharide binding protein (LBP) and cell surface expressed CD14. Whether macrophage (M phi) recognize and respond to LPS in a similar manner is unknown. Here we show that human monocyte derived M phi respond to LPS by tumor necrosis factor alpha release and procoagulant activity upregulation by a similar dose response curve in the presence or absence of serum: suggesting that humoral factors such as LBP are relatively unimportant in the activation of M phi. Both serum dependent and serum independent activation of M phi by LPS require cellular CD14, as evidenced by blocking studies with CD14 specific antibodies. Clones from the monocytoid cell line Mono Mac 6 selected for high LPS sensitivity displayed similar properties. When washed free of serum and cultured in the presence of calcitriol, they responded to LPS in a similar manner, regardless of the presence or absence of serum, and this response was inhibited by anti CD14. It is hypothesized that during their differentiation, M phi acquire a functional substitute for the serum factor LBP, thereby being able to recognize low LPS concentrations in a milieu low in LBP concentration. It will be of interest to determine whether this is a high affinity LBP receptor, LBP itself, or another cell surface constituent.