GLYCOSYL-PHOSPHATIDYLINOSITOL-ANCHORED OR INTEGRAL MEMBRANE FORMS OF CD14 MEDIATE IDENTICAL CELLULAR-RESPONSES TO ENDOTOXIN

Endotoxin stimulates leukocytes to release cytokines that initiate sep tic shock in humans and animals. CD14, a glycosyl-phosphatidylinositol -anchored membrane glycoprotein, is an endotoxin receptor on leukocyte s, and endotoxin binding to CD14 induces cytokine production. Here we show that glycosyl-phosphatidylinositol-anchored or integral membrane CD14 mediates identical cellular responses to endotoxin, including NF- kappaB activation and protein tyrosine phosphorylation. We also show t hat an anti-CD14 monoclonal antibody that does not block endotoxin bin ding to CD14 nonetheless inhibits cell activation by endotoxin. These findings suggest that binding of endotoxin to cell-surface CD14 is fol lowed by subsequent interactions of the endotoxin-CD14 complex with ad ditional membrane component(s) that enable transmembrane signaling. Th is function of CD14 may be prototypic for other members of the glycosy l-phosphatidylinositol-anchored family of proteins that do not play a primary role in signal transduction but rather are the principal ligan d-binding units of membrane-bound receptor complexes.