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 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 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.
Shi
R J
RJ
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York, USA.
Simpson-Haidaris
P J
PJ
Marder
V J
VJ
Silverman
D J
DJ
Sporn
L A
LA
D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D012373:Rocky Mountain Spotted Fever / Q000378:metabolism* / Q000473:pathology
D003470:Culture Media; D017395:Plasminogen Activator Inhibitor 1