RECOMBINANT SOLUBLE CD14 INHIBITS LPS-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY CELLS IN WHOLE-BLOOD

CD14 functions as a cell surface receptor for LPS in the activation of monocytes/macrophages and neutrophils by endotoxin. To assess the uti lity of soluble forms of the CD14 receptor as a possible therapeutic f or endotoxin shock, we have produced recombinant human soluble CD14 us ing a baculovirus expression system. We find that the recombinant prot ein is not only expressed on the surface of the insect cells as a glyc osyl phosphatidylinositol (GPI)-anchored protein, but is also released into the culture medium as a soluble form that lacks the GPI anchor. Functional analyses of recombinant human soluble CD14 show that it bin ds specifically to LPS and can inhibit the LPS-induced release of TNF- alpha by macrophages and mononuclear cells as well as by cells in whol e human blood when used at concentrations of approximately 70 mu g/ml. Thus, soluble CD14 may be useful as an adjunct in the treatment of en dotoxin shock.