Neutrophil response to Neisseria meningitidis: inhibition of adhesion molecule expression and phagocytosis by recombinant bactericidal/permeability-increasing protein (rBPI21).
Polymorphonuclear neutrophil (PMNL) activation enhances microbial clearance but also contributes to the vascular damage and multiorgan failure associated with severe meningococcal sepsis. By use of a whole blood model of meningococcal bacteremia, loss of PMNL L-selectin and up-regulation of CD11b was observed in response to Neisseria meningitidis serogroups B and C, which is followed by opsonophagocytosis. PMNL priming with either Escherichia coli lipopolysaccharide (LPS) or FMLP prior to meningococcal challenge resulted in enhancement of both PMNL L-selectin shedding (1.5- to 4-fold) and phagocytosis (2- to 3-fold). Blockade of meningococcal LPS lipid A with recombinant bactericidal/permeability-increasing protein (rBPI21) resulted in partial inhibition of the PMNL activation and phagocytosis response to N. meningitidis. The effect of rBPI21 was reversed by excess E. coli LPS or FMLP. It is proposed that PMNL priming by N. meningitidis results in an exaggerated activation and phagocytosis response to the organism.
Heyderman
R S
RS
Division of Microbiology, Departments of Pathology and Microbiology, School of Medical Sciences, University of Bristol, University Walk, Bristol, United Kingdom BS8 1TD. r.heyderman@bristol.ac.uk
Ison
C A
CA
Peakman
M
M
Levin
M
M
Klein
N J
NJ
D000328:Adult; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008565:Membrane Proteins / Q000494:pharmacology*; D008589:Meningococcal Infections / Q000276:immunology* / Q000382:microbiology; D009345:Neisseria meningitidis / Q000276:immunology*; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects*
D015815:Cell Adhesion Molecules; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; C025357:endotoxin binding proteins; D019041:L-Selectin