Summary
Changes in PAI-1 expression in human umbilical vein endothelial cells (HUVEC) were
studied following in vitro infection with Rickettsia rickettsii. A 1.8-fold increase
in secreted PAI-1 activity occurred in infected versus control cultures (p = 0.03)
at 24 h but not at earlier timepoints. 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 35S-methionine concurrent with R. rickettsii infection. Such infection resulted in a
1.9-fold increase in labeled PAI-1 in the medium at 24 h (p = 0.036). Increase in
steady-state levels of PAI-1 mRNA were detected as early as 18 h by Northern blot
analysis, peaking (5.5-fold) at approximately 24 h. These results indicate that PAI-1
production is increased in RR-infected endothelial cells, an effect that may contribute
to the vascular occlusions noted in Rocky Mountain spotted fever.
