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Rickettsia rickettsii infection of cultured endothelial cells induces
release of large von Willebrand factor multimers from Weibel-Palade bodies
LA Sporn, RJ Shi, SO Lawrence, DJ Silverman and VJ Marder
Department of Medicine, University of Rochester School of Medicine &
Dentistry, NY.
The clinical manifestations of Rocky Mountain spotted fever (RMSF) result
from Rickettsia rickettsii (R rickettsii) infection of endothelial cells
and are mediated by pathologic changes localized to the vessel, including
in situ thrombosis and tissue ischemia. This study uses in vitro infection
of cultured human umbilical vein endothelial cells with R rickettsii to
test the hypothesis that such infection induces von Willebrand factor (vWF)
release from Weibel- Palade bodies, a process that could contribute to
thrombotic changes. At 24 hours postinfection, there was an increase in
metabolically prelabeled large multimers of vWF in the culture medium, with
a concomitant decrease of these forms in the cell lysate samples. This
release reaction was specific for the large multimer pool of vWF, localized
to Weibel-Palade bodies, because no change in the distribution of dimeric
forms between cells and culture medium was detected. Double-label
immunofluorescence staining showed an inverse correlation between the
number of R rickettsii and the number of Weibel- Palade bodies in infected
cells. Cell lysis was minimal at 24 hours postinfection, as no detectable
intracellular precursor forms (molecular weight 260,000) of vWF were
released into the culture medium, there was no decrease in cell viability
as measured by trypan blue exclusion, and no increase in 51Cr-release into
the culture medium was observed when compared with uninfected controls.
Release was likely a direct effect of the intracellular presence of the
organism, rather than due to a noxious soluble factor such as endotoxin,
because culture medium conditioned by infected endothelial cells was
ineffective at inducing release in uninfected endothelial cell cultures. In
summary, in vitro infection of endothelial cells by R rickettsii induces
release of Weibel-Palade body contents, a process that may contribute to
the pathogenesis of RMSF.
Volume 78,
Issue 10,
pp. 2595-2602,
11/15/1991
Copyright © 1991 by The American Society of Hematology
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