# RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1988 · $127,644

## Abstract

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is
considered the most severe of the human rickettsioses.  The putative target
cells of infection are the endothelial cell and occasionally smooth muscle
cells of small blood vessels.  The primary purpose of this investigation is
to determine the specific mechanism of cell injury to human vascular
endothelial cells cause by R. rickettsii, and to examine the potential
biological ramifications of platelet adherence to infected endothelial
cells.  Understanding of the mechanism of cell injury by R. rickettsii and
the consequences of platelet adherence to a normally non-thrombogenic
surface should contribute considerably to a better undertanding of the
pathogenesis of RMSF, and could provide for more specific therapeutic
management of severe forms of the disease.

This study will be carried out exclusively in human endothelial cells
derived from the umbilical vein using combined biochemical and electron
microscopic techniques.  The hypothesis that endothelial cell injury caused
by R. rickettsii is the direct result of intracellular rickettsial
metabolism, will be tested.  Specifically, that lipid peroxidation of
intracellular membranes by toxic free radicals leads to dilatation and
disorganization of the ER and eventually to lysis of the cell.  Analysis of
levels of malonaldehyde, the primary degradation product of peroxidation,
and superoxide anion and superoxide dismutase will be carried out as well
as the activity of two ER membrane markers, glucose-6-phosphatase and
cytochrome P-450 which are destroyed as a result of peroxidation.  Steroids
and the antitoxidants glutathione and vitamin E will be examined for their
protective capacity as free radical scavengers.  The effects of superoxide
dismutase incorporated into unilamellar liposomes and added to R.
rickettsii-infected endothelial cells will be studied to determine whether
cell injury caused by the organisms can be modified.  Studies on platelet
adherence using [3H] adenine and scanning electron microscopy, and the
activation status of adherent platelets using [3H] serotonin will also be
studied.  Lastly, as a prelude to a future study, an attempt will be made
to isolate and characterize plasmid DNA from R. rickettsii.

## Key facts

- **NIH application ID:** 3127214
- **Project number:** 5R01AI017416-06
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** DAVID J SILVERMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $127,644
- **Award type:** 5
- **Project period:** 1980-12-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127214

## Citation

> US National Institutes of Health, RePORTER application 3127214, RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS (5R01AI017416-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127214. Licensed CC0.

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