A RECOMBINANT AMINO-TERMINAL FRAGMENT OF BACTERICIDAL PERMEABILITY-INCREASING PROTEIN (RBPI23) INHIBITS SOLUBLE CD14-MEDIATED LIPOPOLYSACCHARIDE-INDUCED ENDOTHELIAL ADHERENCE FOR HUMAN NEUTROPHILS

Exposure of cultured human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) or interleukin 1 (IL-1) causes increased expression of adhesion molecules such as E-selectin and CD54 by HUVEC and consequently increased adherence of peripheral blood neutrophils. A recombinant amino-terminal fragment of bactericidal/permeability increasing protein (rBPI23) was shown to specifically block the LPS-induced adhesiveness of HUVEC for neutrophils. rBPI23 also prevented the LPS- but not IL-1beta-induced upregulation on HUVEC of E-selectin and CD54. Furthermore, this inhibition was evident even when the endothelial cells were exposed to LPS for up to 1-2 h prior to rBPI23 addition. The inhibitory effects of an anti-CD14 monoclonal antibodies (mAb) were similar to those of rBPI23. Combination of the anti-CD14 mAb and rBPI23 resulted inhibition greater than either one used alone. These studies demonstrate that rBPI23 acts as a specific and potent inhibitor of soluble CD14-mediated LPS induction.