Haemophilus influenzae type b lipooligosaccharide induces meningeal inflammation.
We evaluated the ability of two Haemophilus influenzae type b (Hib) components, lipooligosaccharide (LOS) and capsular polysaccharide, to provoke meningeal inflammation in rabbits. Intracisternal inoculation of 2 fg-200 ng of LOS produced a dose-dependent increase in concentrations of white blood cells and protein in cerebrospinal fluid, whereas 4 micrograms of Hib capsular polysaccharide did not provoke meningeal inflammation. Preincubation of LOS with a murine monoclonal antibody to Hib LOS did not reduce the potency of the LOS. Incubation of LOS with polymyxin B (which neutralizes LOS by binding to its lipid A region) and deacylation of the LOS with acyloxyacyl hydrolase (a neutrophil enzyme that removes nonhydroxylated fatty acyl chains from lipid A) reduced meningeal inflammation. We demonstrated that purified Hib LOS induced meningeal inflammation in this model and suggest that the lipid A moiety of Hib LOS is principally responsible for this host response.
Syrogiannopoulos
G A
GA
Department of Pediatrics, Southwestern Medical School, Dallas, Texas 75235.
Hansen
E J
EJ
Erwin
A L
AL
Munford
R S
RS
Rutledge
J
J
Reisch
J S
JS
McCracken
G H
GH
D000704:Analysis of Variance; D000818:Animals; D016667:Bacterial Capsules; D001428:Bacterial Vaccines; D001921:Brain / Q000473:pathology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D004195:Disease Models, Animal; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000134:cerebrospinal fluid*; D008297:Male; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000473:pathology; D011135:Polysaccharides, Bacterial / Q000134:cerebrospinal fluid; D011817:Rabbits; D012044:Regression Analysis
D001428:Bacterial Vaccines; D002556:Cerebrospinal Fluid Proteins; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; C023023:lipid-linked oligosaccharides