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

Using human umbilical vein endothelial cells as an in vitro model of toxicity, it was found that Neisseria meningitidis, Neisseria gonorrhoeae, Neisseria lactamica and Neisseria sicca caused damage to these cells, in contrast to the lack of cytotoxicity exhibited by Haemophilus influenzae 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 be inhibited by polymyxin B, suggesting that lipopolysaccharide plays a major role in toxicity. However, the toxicity mediated by lipopolysaccharide was modulated significantly by pilus-dependent adherence. Intra-strain variants expressing altered pilins which exhibited different levels of adherence to epithelial and endothelial cells were used to study the role of pilus. The degree of toxicity observed correlated with their relative level of adherence to cultured cells. In contrast, Ope-dependent increased adherence did not result in increased toxicity for endothelial cells, suggesting that pill have a synergistic effect, contributing to the overall damage.