Endothelial prostaglandin secretion: effects of typhus rickettsiae.

Cultured human umbilical vein-derived endothelial cells were incubated with typhus rickettsiae, and supernatants were examined for the presence of prostaglandins I2 (PGI2) and E2 (PGE2). Cells incubated with metabolically active rickettsiae secreted significantly more PGI2 and PGE2 than did those incubated with buffer alone or with killed rickettsiae. The amount of PGI2 secreted was directly related to the number of hemolytically active rickettsiae present; abolishing rickettsial hemolytic activity abolished their effect on PGI2 secretion. Mice injected with a lethal dose of native typhus rickettsiae exhibited a rapid rise in circulating PGI2 levels; mice given hemolytically inactive rickettsiae survived and exhibited no rise in plasma PGI2 levels. Finally, endothelial cells were infected with rickettsiae, and secretion of prostaglandins was monitored during rickettsial multiplication; intracellular accumulation of rickettsiae resulted in endothelial destruction and a dramatic increase in endothelial secretion of PGI2 and PGE2. Therefore, typhus rickettsiae can increase endothelial secretion of arachidonate-derived autocoids.