DUAL EFFECTS OF SOLUBLE CD14 ON LPS PRIMING OF NEUTROPHILS

To evaluate the effect of soluble CD14 (sCD14) on human neutrophil res ponse to lipopolysaccharide (LPS), we developed an LPS-priming assay t hat measures the chemiluminescence response to N-formyl-methionyl-leuc yl-phenylalanine stimulation, Priming by 1 ng/mL rough LPS occurred in the presence of either serum or recombinant LPS-binding protein (LBP) only, Priming was completely CD14-dependent because preincubation of the neutrophils with an anti-CD14 monoclonal antibody prevented primin g, We hypothesize that sCD14 enhances LPS response in neutrophils, but this response is not as effective as LPS response via membrane CD14 ( mCD14). In our experiments sCD14 is present in an excess compared with mCD14. Priming of neutrophils occurs with low LBP, supposedly via sCD 14-LPS complexes, With high LBP, addition of sCD14 inhibited LPS-primi ng of neutrophils, In that case, LPS may be transported to sCD14, prev enting a more effective response via mCD14. In this study we demonstra te that the effect of sCD14 on neutrophil response to LPS is a delicat e balance between activation and inhibition depending on concentration of serum or LBP.