Enhancement of Ca^<2+>-influx and prostaglandin E_2accumulation in cultured pig vascular smooth muscle cells infected with Salmonella Choleraesuis

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Three clinical distinguishable forms of salmonellosis, enteric fever (typhoid fever and paratyphoid fever), septicemia and acute gastroenteritis occur in humans. Salmonella septicemia in humans are most commonly caused by S.Choleraesuis, a swine-adaped serotype of Salmonella. Our previous reports has shown that S.Choleraesuis strain RF-1 caused septicemia and killed pigs with severe hemorrhages on whole body. This results suggested that S.Choleraesuis caused lesions of the vascular tissues, which developed the hemorrhages in the infected pigs. In the present study, in vitro effects of S.Choleraesuis on cultured vascular smooth musle cells prepared from aortas of pigs were examined.S.Choleraesuis strain-RF-1 was observed to invade the vascular smooth muscle cells after 3 to 5 hours incubation in a time-dependent manner. RF-1 strain contracted the vascular smooth muscle cells in parallel with the increase of inyasion. This morphological change was diminished by incubation of the vascular … More smooth muscle cells with a invA mutant (a invasion-deficient derivative) of RE-1 strain. Accompanying the contraction, both influx of Ca^<2+> and activity of phopholipase A_2(PLA_2) activity were increased in the cells incubated with RF-1 atrain, but not with invA mutant, suggesting that the arachidonic acid cascades were activated by the invasion of S.Choleraesuis. Then we analyzed the metabolites of arachidonic acid, prostaglandins (PGs) and leukotriens (LTs), in the vascular smooth muscle cells. It was demonstrated that the cellular contents of PGE_2 remarkably increased in the cells by the invasion of RF-1 strain. However, the contents of neither LTC_4, LTD_4 nor LTE_4 were influenced. Our results showed that invasion of S.Choleraesuis enhanced Ca^<2+> influx and activated PLA_2 resulting in the accumulation of cellular PGE_2 in the vascular smooth muscle cells. The increase of PGE_2 could cause the contraction of vascular smooth muscle cells, which may lead to the lesions of the vascular tissues of pigs infected with S.Choleraesuis. Less