LPS INDUCES CD14 ASSOCIATION WITH COMPLEMENT RECEPTOR-TYPE 3, WHICH IS REVERSED BY NEUTROPHIL ADHESION

CD14, a glycosylphosphatidyl inositol (GPI)-linked membrane protein, i s a key membrane binding site for LPS (endotoxin). Although CD14 lacks transmembrane and cytoplasmic sequences, it activates CR3-mediated le ukocyte adhesion and cytokine release, Since CR3 has been shown to int eract with other GPI-linked membrane proteins, we tested the hypothesi s that CD14 can physically associate with CR3, Using qualitative and q uantitative resonance energy transfer microscopy, we show that LPS in the presence of serum or LPS binding protein triggers formation of CD1 4-CR3 complexes, Kinetic studies show that CD14-CR3 complexes dissocia te as neutrophils attach to substrates, We speculate that LPS-charged CD14 enhances CR3-mediated adhesion by directly binding to CR3.