Human endothelial cell culture plaques induced by Rickettsia rickettsii

Walker, David H.; Firth, William T.; Edgell, Cora Jean S.

doi:10.1128/iai.37.1.301-306.1982

Cited by 37 publications

(12 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This study indicates that this in vivo predilection of rickettsiae for EC is probably not due to an unusual avidity of rickettsiae for EC or an increased susceptibility of EC to rickettsial infection; rickettsiae entered EC and fibroblasts similarly during a 60-min incubation. This observation is consistent with the report of Walker et al (30) that R.…”

Section: Walkersupporting

confidence: 94%

Rickettsial interactions with human endothelial cells in vitro: adherence and entry

Walker¹

1984

Infect Immun

View full text Add to dashboard Cite

Rickettsia prowazekii, Madrid E strain, was assessed for its ability to enter endothelial cells derived from the veins of human umbilical cord in vitro. Rickettsial entry increased linearly with multiplicity of infection up to a multiplicity of 500; thereafter, additional rickettsiae adhered, but without a concomitant increase in the number of intracellular rickettsiae. Rickettsial entry required participation both of rickettsiae and endothelial cells; inactivation of rickettsiae with N-ethylmaleimide or Formalin, or of endothelial cells with cytochalasin B or D or NaF greatly reduced rickettsial entry. Because rickettsiae adhered to inactivated endothelial cells, adherence could be examined in the absence of entry. Rickettsial adherence was inhibited by poisons that inhibited rickettsial hemolysis. Calcium ionophore A23187, which did not inhibit endothelial pinocytosis, stimulated rickettsial adherence to endothelial cells, but inhibited rickettsial entry. These results indicated that typhus rickettsiae entered endothelial cells via induced phagocytosis, and that the signal for entry, which was dependent upon rickettsial energy, probably involved formation of a calcium gradient.

show abstract

Section: Walkersupporting

confidence: 94%

Rickettsial interactions with human endothelial cells in vitro: adherence and entry

Walker¹

1984

Infect Immun

View full text Add to dashboard Cite

show abstract

“…Rickettsiae are intracellular bacteria living free in the cytosol of infected cells. The endothelial cells (EC) represent the target cells of rickettsiae in human infections (22,25,30,31). EC infection results in vascular injury to small blood vessels (32).…”

mentioning

confidence: 99%

von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells

et al. 1992

View full text Add to dashboard Cite

Mediterranean spotted fever, a tick-borne rickettsiosis caused by Rickettsia conorii, may lead to small-vessel or deep-vein thrombosis. In order to evaluate the role of endothelial cell alteration in this lesion, we infected human endothelial cells derived from umbilical veins with R. conorii. We report the induction of two previously unreported prothrombotic mechanisms in rickettsial disease: (i) a progressive decline in thrombomodulin antigen and (ii) early expression of tissue factor, and, as described for R. rickettsii infection, later release of von Willebrand factor from Weibel-Palade bodies. Thrombomodulin expression in infected endothelial cells, measured by the thrombin-dependent activation of protein C or flow cytometric analysis, decreased steadily between 4 and 24 h after inoculation with rickettsiae. R. conorii infection induced tissue factor expression, measured by clotting assay and flow cytometric analysis, which was detectable 2 h postinoculation, reached its maximum 4 h postinoculation, and progressively decreased thereafter. Infection resulted in a relatively late release ofvon Willebrand factor antigen into the culture medium. A double-label immunofluorescence assay for the simultaneous evaluation of von Willebrand factor and R. conorii showed that the depletion of cytoplasmic von Willebrand factor stored in Weibel-Palade bodies was due to a direct effect of the intracellular R. conorii. These disturbances of endothelial function observed with R. conorii-infected cells may provide a paradigm for the elucidation of thrombotic pathobiology with Mediterranean spotted fever.

show abstract

“…HUVECs are a standardized model for early responses to rickettsial vascular infection. 35 To understand the spectrum of proteins secreted/released by endothelial cells in response to R. conorii infection, a quantitative proteomics analysis of the proteins in the conditioned medium of HUVECs with and without R. conorii infection was conducted ( Figure 1). The mass spectrometry raw data and proteomics have been deposited in the ProteomeXchange Consortium via the PRIDE 36 partner repository (https://www.ebi.ac.uk/pride/ archive; data set identifier PXD013548).…”

Section: Quantitative Proteomics Analysis Of Secretome Of Huvecs Infementioning

confidence: 99%

Quantitative Proteomics of the Endothelial Secretome Identifies RC0497 as Diagnostic of Acute Rickettsial Spotted Fever Infections

Zhao

Fang

Zhang

et al. 2020

The American Journal of Pathology

View full text Add to dashboard Cite

Mediterranean spotted fever is a reemerging acute tick-borne infection produced by the a-proteobacterium, Rickettsia conorii. Rickettsia conorii infects vascular endothelial cells producing disseminated plasma leakage, manifesting as nonspecific fever, headache, and maculopapular rash. Because there are no available tests of early infection, Mediterranean spotted fever is often undiagnosed and untreated, resulting in significant mortality. To address this critical need, we have applied a quantitative proteomics pipeline for analyzing the secretome of primary human umbilical vein endothelial cells. Of the 104 proteins whose abundance changed significantly in the R. conoriieinfected human umbilical vein endothelial cells' secretome, 46 proteins were up-regulated: 45 were host secreted proteins (including cytokines), and 1 was a rickettsial protein, the putative N-acetylmuramoyl-L-alanine amidase RC0497. Proteins with sequence highly homologous to RC0497 were found to be shared by many species of the spotted fever group rickettsiae, but not typhus group rickettsiae. Quantitative targeted proteomics studies of plasma from a mouse model of sublethal and lethal R. conorii identified RC0497 in the blood, and its circulating levels were proportionally associated with infection outcome. Finally, the presence of RC0497 in the serum samples from a cohort of humans presenting with acute rickettsioses was confirmed. The detection of RC0497 has the potential to be a sensitive and specific marker for acute rickettsial spotted rickettsioses. (Am J Pathol 2020, 190: 306e322; https://doi.

show abstract

Human endothelial cell culture plaques induced by Rickettsia rickettsii

Cited by 37 publications

References 19 publications

Rickettsial interactions with human endothelial cells in vitro: adherence and entry

Rickettsial interactions with human endothelial cells in vitro: adherence and entry

von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells

Quantitative Proteomics of the Endothelial Secretome Identifies RC0497 as Diagnostic of Acute Rickettsial Spotted Fever Infections

Contact Info

Product

Resources

About