# RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1990 · $169,429

## Abstract

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is
considered the most severe of the human rickettsioses. Usually transmitted
by the bite of a tick, the organisms are introduced during a blood meal
directly beneath the skin where they invade and destroy the endothelial
cells of small blood vessels. Our laboratory has established an in vitro
model to study different parameters of rickettsiae-host interaction
including mechanisms of injury to endothelial cells infected by this
organism. An understanding of the specific mechanism(s) of cell injury
caused by R. rickettsii should significantly enhance existing knowledge of
the pathogenesis of RMSF, and could provide for more specific therapeutic
management of severe forms of the disease.

The proposed study will be carried out primarily in cultured human
endothelial cells derived from the umbilical vein. The cells will be
infected as monolayers by  strains of R. rickettsii of high, intermediate,
or low virulence. Current evidence strongly suggests that R.
rickettsii-induced endothelial cell injury is mediated by free radicals
that cause peroxidation of cell membrane lipids. This hypothesis will be
pursued in the context of : (a) identification of the specific lipid
hydroperoxides formed in infected endothelial cells using high-performance
liquid chromatography; (b) an analysis of strains of R. rickettsii of
varying degrees of virulence and their capacity to infect, replicate, and
injure endothelial cells as determined by microscopic and biochemical
techniques; (c) determination of comparative intracellular levels of
reduced glutathione and the enzymes, catalase and glutathione peroxidase as
a measure of inherent cellular defense mechanisms against oxidative stress;
and (d) the capacity of the glutathione precursor, gamma-glutamylcysteine,
to reduce intracellular peroxide levels and abrogate endothelial cell
injury.

## Key facts

- **NIH application ID:** 3127210
- **Project number:** 2R01AI017416-07A1
- **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:** 1990
- **Award amount:** $169,429
- **Award type:** 2
- **Project period:** 1980-12-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127210

## Citation

> US National Institutes of Health, RePORTER application 3127210, RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS (2R01AI017416-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127210. Licensed CC0.

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