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Rickettsia rickettsii infection of cultured human endothelial cells induces
tissue factor expression
LA Sporn, PJ Haidaris, RJ Shi, Y Nemerson, DJ Silverman and VJ Marder
Department of Medicine, University of Rochester School of Medicine and
Dentistry, NY.
Microvascular thrombi underlie many of the clinical manifestations of Rocky
Mountain spotted fever (RMSF), a disease characterized by Rickettsia
rickettsii infection of vascular endothelial cells. Studies were designed
to determine whether R rickettsii-infection of cultured human umbilical
vein endothelial cells results in tissue factor (TF) induction, a process
that could directly activate coagulation in infected vessels. Whereas
uninfected endothelial cell cultures showed essentially undetectable TF
mRNA and activity, both TF mRNA and activity were present after R
rickettsii infection. TF mRNA levels were transient, peaking at 4 hours
after the initiation of infection, whereas the peak of TF activity occurred
at 8 hours. Induction of the TF response requires the intracellular
presence of R rickettsii organisms, because uninfected rickettsia were
ineffective and the response was blocked by inhibiting rickettsial entry
using cytochalasin B. TF induction was not mediated by endothelial cell
release of soluble factor, because no response was induced using culture
medium conditioned by R rickettsii-infected cells. Furthermore,
preadsorption of suspensions of R rickettsii with polymyxin B to remove
contaminating lipopolysaccharide did not eliminate the TF response.
Induction of TF in vital endothelial cells during R rickettsii infection
could be the trigger for vascular thrombus formation of RMSF.
Volume 83,
Issue 6,
pp. 1527-1534,
03/15/1994
Copyright © 1994 by The American Society of Hematology
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