# ANTIMICROBIAL EFFECT OF PEROXIDASE - ROLE IN LEUKOCYTES

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1987 · $149,044

## Abstract

We propose to study the properties, mechanism of action and biological
significance the oxygen-dependent antimicrobial systems of phagocytes.
Phagocytes respond to perturbation of the plasma membrane with a burst of
oxygen consumption and extra oxygen consumed is converted to the superoxide
anion, hydrogen peroxide, hydroxyl radicals and possible singlet oxygen,
each of which may contribute to themicrobicidal activity of the cells.  the
toxicity of H2O2 is increased considerably by the addition of peroxidase
and a halide and this antimicrobial system appears to play a role in
certain phagocytes (e.g. neutrophils, monocytes).  Our aim is to determine
the mechanism of target cell destruction by these antimicrobial systems
with emphasis on the oxidation of iron centers with the release of iron
into the medium.  Intact organisms, membrane vesicles or model
iron-containing compounds will be exposed to isolated antimicrobial systems
and, in some instances, to intact phagocytes.  The organisms will be
prelabeled with 59Fe, and polyacrylamide gel electrophoresis,
radioautography and histochemical staining will be employed to identify the
proteins primarily affected.  The binding of the released iron by
lactoferrin will be investigated since this iron-binding protein is present
in neutrophil granules and may serve as a biological chelator of the iron
in situ.  The properties of a new iron-containing antimicrobial system
consisting of iron, H2O2 and iodide will be investigated with emphasis on
the usefulness of this system for the disinfection of water of organisms
which induce diarrhea (e.g. Giardia cysts).  A study of the susceptibility
of the intracellular pathogen Mycobacterium leprae to the antimicrobial
systems of phagocytes will be undertaken in an attempt to determine the
basis for their host resistance.  A microscopic and metabolic method for
the rapid detection of viability of M leprae will be evaluated.  Neutrophil
function of selected patients with an increased susceptibility to
infectionwill be evaluated in an attempt to elucidate the basis for the
dysfunction.  The long term goals are 1) to determine the role of these
systems in the killing of microorganisms by phagocytes; 2) to determine
whether alterations in these systems contribute to the pathogenesis of
disease; and 3) to determine whether manipulations of these systems
influence the course of disease.

## Key facts

- **NIH application ID:** 3124387
- **Project number:** 5R01AI007763-21
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** SEYMOUR J KLEBANOFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $149,044
- **Award type:** 5
- **Project period:** 1978-06-01 → 1988-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124387

## Citation

> US National Institutes of Health, RePORTER application 3124387, ANTIMICROBIAL EFFECT OF PEROXIDASE - ROLE IN LEUKOCYTES (5R01AI007763-21). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124387. Licensed CC0.

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