INCREASED EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN R-RICKETTSII-INFECTED ENDOTHELIAL-CELLS

Changes in PAI-1 expression in human umbilical vein endothelial cells (HUVEC) were studied following in vitro infection with Rickettsia rick ettsii. A 1.8-foid increase in secreted PAI-1 activity occurred in inf ected versus control cultures (p = 0.03) at 24 h but not at earlier ti mepoints. A similar increase (1.4-fold) in secreted PAI-1 antigen (p < 0.005) was measured by ELISA. To determine whether this increase was due to increased synthesis of PAI-1, HUVEC were metabolically labeled with S-35-merhionine concurrent with R. rickettsii infection. Such inf ection resulted in a 1.9-fold increase in labeled PAI-1 in the medium at 24 h (p = 0.036). Increase in steady-slate levels of PAI-1 mRNA wer e detected as early as 18 h by Northern blot analysis, peaking (5.5-fo ld) at approximately 21 h. These results indicate that PAI-1 productio n is increased in RR-infected endothelial cells, an effect that may co ntribute to the vascular occlusions noted in Rocky Mountain spotted fe ver.