The role of bacterial lipopolysaccharide-bound neutrophils in the pathogenesis of Kawasaki disease

To investigate the possible role of lipopolysaccharide (LPS, endotoxin) in the pathogenesis of Kawasaki disease, neutrophils from 15 patients with the disease and 7 with sepsis (4 infected with gram-negative bacteria and 3 wi th gram-positive bacteria) were analyzed by flow cytometry using anti-LPS a nd anti-CD14 monoclonal antibodies. The number of LPS- and CD14-positive ne utrophils was dramatically higher early after the onset of Kawasaki disease and gram-negative sepsis but not with gram-positive sepsis. An immunopreci pitation analysis revealed LPS was bound to CD14 in vivo on neutrophils fro m Kawasaki disease patients. The mean plasma level of neutrophil elastase w as significantly higher in the acute phase of Kawasaki disease than in the acute phase of sepsis. These findings suggest that exposure to LPS occurs a t the onset of Kawasaki disease when LPS-bound neutrophils secrete excess p rotease (implicated in neutrophil-mediated endothelial injury) into the cir culation.