# RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1993 · $280,347

## Abstract

DESCRIPTION (Adapted from the Applicant's Abstract):  Rocky Mountain
spotted  fever, caused by Rickettsia rickettsii, is an important
infection in the  United States owing to the extreme severity of
untreated cases, the difficulty  in establishing an early clinical or
laboratory diagnosis, and the lack of an  effective means of prevention.
Transmitted by tick bite, the organisms are  spread by the bloodstream
throughout the body, entering and injuring endothelial cells of the
microcirculation.

The in vitro model of Rickettsia rickettsii endothelial cell interaction
utilized in Dr. Silverman's laboratory has led during the current funding
cycle to highly productive research with establishment of important new
concepts of infectious disease pathogenesis.  The proposed study will
examine  cultured human endothelial cells infected with the virulent
Sheila Smith  strain and the avirulent Iowa strain of R. rickettsii and
the virulent Breinl  and avirulent Madrid E strains of R. prowazekii.
Current evidence from  Dr. Silverman's laboratory  strongly suggests that
R. rickettsii induced  endothelial cell injury is mediated by reactive
oxygen species.  Superoxide  radical has been detected in large amounts
in culture supernatants during  internalization of rickettsiae into
endothelial cells.  The investigator  postulates that injury is initiated
as a result of aborted phagocytosis of the  organism that results in an
oxidative burst.  The oxidative burst releases  superoxide at the cell
surface which is converted to toxic H202 by extracellular superoxide
dismutase in the endothelial glycocalyx.  H202  readily passes through
the plasma membrane and is capable of directly causing  peroxidation of
membrane lipids, or it may react with additional superoxide to  produce
the even more toxic hydroxyl radical.  Catalase and pyruvate are known
scavengers of H202 and protect endothelial cells from hydrogen peroxide
generated from superoxide.  The hypothesis that R. rickettsii causes
abortive  phagocytosis leading to endothelial cell injury following
pretreatment with  these scavengers, measuring intracellular glutathione
and comparing them to  comparable experiments with the Iowa, Breinl and
Madrid E strains.

## Key facts

- **NIH application ID:** 3127211
- **Project number:** 2R01AI017416-10
- **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:** 1993
- **Award amount:** $280,347
- **Award type:** 2
- **Project period:** 1980-12-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127211

## Citation

> US National Institutes of Health, RePORTER application 3127211, RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS (2R01AI017416-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127211. Licensed CC0.

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