# MOLECULAR BASIS FOR MICROBICIDAL ACTION IN LEUKOCYTES

> **NIH NIH R01** · OREGON GRADUATE INSTITUTE SCIENCE & TECH · 1988 · $149,275

## Abstract

Studies are proposed to identify oxidative reactions occurring in
phagocytosing leukocytes that are associated with microbicidal action.  We
have shown that the oxidant, hypochlorous acid (HOC1), inactivates E. coli
in reactions that lead to destruction of metabolic energy reserves within
the cell and to loss of energy-linked functions such as active transport.
To explore the underlying molecular mechanisms, membrane localized
energy-linked systems, including the ATP synthetase and selected ion and
metabolite transport proteins, will be examined for evidence of oxidative
damage.  Studies to identify the lethal reactions of hydroxyl radical (OH)
or OH-radical-generating systems willl be initiated.  Comparison will be
made between cell viabilities and loss of specific metabolic functions or
biochemical components to identify loci of oxidative attack associated with
cellular death.  For this purpose differing methods of forming hydroxyl
radical will be used that allow its generation in the extracellular medium,
at the cell usrface, or within the microbial cell.  Following protocols
developed for study of inactivation by HOC1, the consequences of OH
oxidation upon cellular transport systems, nucleotide concentrations,
protonmotive force, and respiratory components (when appropriate) will be
determined.  For both HOC1 and OH oxidations, various organisms with widely
differing metabolic requirements and cellular topographic organization will
be studied to determine if particular inactivation mechanisms are
"universal" in character.  Organisms exhibiting clearly different
mechanisms of oxidative inactivation by HOC1 and OH will be used to
identify the toxin produced in neutrophil phagosomes.  For these
experiments the microbes will be phagocytosed, then immediately recovered
to determine the cause of death.  These studies should greatly clarify the
nature of leukocytic mechanisms comprising host response to infection.

## Key facts

- **NIH application ID:** 3126451
- **Project number:** 5R01AI015834-09
- **Recipient organization:** OREGON GRADUATE INSTITUTE SCIENCE & TECH
- **Principal Investigator:** JAMES K HURST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $149,275
- **Award type:** 5
- **Project period:** 1979-04-01 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126451

## Citation

> US National Institutes of Health, RePORTER application 3126451, MOLECULAR BASIS FOR MICROBICIDAL ACTION IN LEUKOCYTES (5R01AI015834-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126451. Licensed CC0.

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