Cytotoxicity of Vibrio vulnificus cytolysin on rat peritoneal mast cells

Histamine has been thought to be a permeability enhancing factor in Vibrio vulnificus infection. The injection of living bacteria or purified V. vulni ficus cytolysin (WC) can cause lethality in mice by inducing hemoconcentrat ion and increased vascular permeability, In the present study, we tried to identify whether histamine release causes the increased vascular permeabili ty that is responsible for the lethal effect of WC, Treatment of rat perito neal mast cells with high concentrations of WC caused the release of whole cellular histamine and lactate dehydrogenase (LDH), At concentrations less than 10 HU/ml, histamine and LDH were not released whereas preloaded a-deox y-D-glucose was rapidly effluxed with the concomitant decrease in cellular ATP, VVC-treated mast cells were refractory to the stimulation of histamine secretion by Compound 48/80 but remained fully responsive to Ca2+ plus GTP -gamma-S, These results indicate that histamine can be released from mast c ells only when the concentration of WC is high enough to cause the lysis of cells. At low concentrations, WC does not induce the release of stored his tamine from damaged cells. The intravenous injection of 80 HU purified WC t o rats, which can produce the calculated blood concentration of about 3 HU/ ml, caused a marked increase in pulmonary vascular permeability, hemoconcen tration and death. However, no increase in blood histamine level was detect ed. This level of WC in rat blood was enough to cause severe hemoconcentrat ion and lethality but might not be enough to cause cytolysis of the mast ce lls and resulting histamine release.