Endothelial adhesion molecule expression and its inhibition by recombinantbactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidis

Vascular endothelial injury is responsible for many of the clinical manifes tations of severe meningococcal disease. Binding and migration of activated host inflammatory cells is a central process in vascular damage. The expre ssion and function of adhesion molecules regulate interactions between leuk ocytes and endothelial cells. Little is known about how meningococci direct ly influence these receptors. In this study we have explored the effect of Neisseria meningitidis on endothelial adhesion molecule expression and foun d this organism to be a potent inducer of the adhesion molecules CD62E, ICA M-1, and VCAM-1. Exposure of endothelium to a serogroup B strain of Neisser ia meningitidis, B1940, and a range of isogenic mutants revealed that lipoo ligosaccharide (LOS) structure and capsulation influence the expression of adhesion molecules. Following only a brief exposure (15 min) to the bacteri a, there were large differences in the capacity of the different mutants to induce vascular cell adhesion molecules, with the unencapsulated and trunc ated LOS strains being most potent (P < 0.05). Furthermore, the pattern of cell adhesion molecule expression was different with purified endotoxin fro m that with intact bacteria. Meningococci were more potent stimuli of CD62E expression than was endotoxin, whereas endotoxin was at least as effective as meningococci in inducing ICAM-1 and VCAM-1. The effect of bactericidal/ permeability increasing protein (rBPI(21)), an antibacterial molecule with antiendotoxin properties, was also dependent on LOS structure. The strains which possessed a truncated or nonsialylated LOS, whether capsulated or not , were more sensitive to the inhibitory effects of rBPI(21). These findings could have important implications for the use of antiendotoxin therapy in meningococcal disease.