Neutrophil response to Neisseria meningitidis: Inhibition of adhesion molecule expression and phagocytosis by recombinant bactericidal permeability-increasing protein (rBPI(21))

Polymorphonuclear neutrophil (PMNL) activation enhances microbial clearance but also contributes to the vascular damage and multiorgan failure associa ted with severe meningococcal sepsis. By use of a whole blood model of meni ngococcal bacteremia, loss of PMNL L-selectin and up-regulation of CD11b wa s observed in response to Neisseria meningitidis serogroups B and C, which is followed by opsonophagocytosis, PMNL priming with either Escherichia col i lipopolysaccharide (PS) or FMLP prior to meningococcal challenge resulted in enhancement of both PMNL L-selectin shedding (1.5- to 4-fold) and phago cytosis (2- to S-fold), Blockade of meningococcal LPS lipid A with recombin ant bactericidal/permeability-increasing protein (rBPI(21)) resulted in par tial inhibition of the PMNL activation and phagocytosis response to N. meni ngitidis. The effect of rBPI(21) was reversed by excess E. coli LPS or FMLP . It is proposed that PMNL priming by N. meningitidis results in an exagger ated activation and phagocytosis response to the organism.