INVESTIGATIONS INTO THE MOLECULAR-BASIS OF MENINGOCOCCAL TOXICITY FORHUMAN ENDOTHELIAL AND EPITHELIAL-CELLS - THE SYNERGISTIC EFFECT OF LPS AND PILI

Using human umbilical vein endothelial cells as an in vitro model of t oxicity, it was found that Neisseria meningitidis, Neisseria gonorrhoe ae, Neisseria lactamica and Neisseria sicca caused damage to these cel ls, in contrast to the lack of cytotoxicity exhibited by Haemophilus i nfluenzae type b. N. meningitidis was also found to be toxic for human epithelial cells. The major toxic factor of N, meningitidis was found to be a heat-stable component of outer membrane vesicles, and could b e inhibited by polymyxin B, suggesting that lipopolysaccharide plays a major role in toxicity. However, the toxicity mediated by lipopolysac charide was modulated significantly by pilus-dependent adherence. Intr a-strain variants expressing altered pilins which exhibited different levels of adherence to epithelial and endothelial cells were used to s tudy the role of pilus. The degree of toxicity observed correlated wit h their relative level of adherence to cultured cells. In contrast, Op e-dependent increased adherence did not result in increased toxicity f or endothelial cells, suggesting that pill have a synergistic effect, contributing to the overall damage.