# PULMONARY AND SYSTEMIC KILLING OF OPPORTUNISTIC FUNGI

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CENTER HOSP · 1993 · $360,702

## Abstract

DESCRIPTION:  (Adapted from applicant's abstract) Opportunistic mycoses
continue to increase in frequency and importance.  In 3 of the most common
of these, candidiasis, aspergillosis, and mucormycosis, hyphae must be
cleared from lesions, primarily by neutrophils (PMN), to prevent
progressive disseminated infections.  These studies focus upon a stepwise
analysis of interactions between fungal hyphae and PMN that ultimately
result in killing of the organisms.  Initially, experiments will
concentrate on interactions os PMN with Candida albicans, with additional
studies using Aspergillus fumigatus and Rhizopus oryzae for specific
aspects likely to differ, if time permits.  Opsonized and unopsonized
hyphae elicit different patterns of early PMN responses leading to
activation of the PMN respiratory burst that is required for hyphal
killing.  Previous data provide initial clues to the identity of apparently
separate PMN binding and activation sites as well as interacting ligands on
opsonized and unopsonized hyphae.  These will be further pursued using
specific MAbs combined with hyphae selectively opsonized with individual
serum factors reactive with PMN receptors.  Activation of specific
receptors will be linked to initiation of early PMN ion fluxes and
biochemical events to determine events and pathways necessary and
sufficient for activation of the respiratory burst and degranulation.
Recent data imply that both are required for fungicidal effects.
Identification of pathways for initial PMN activation will continue,
including studies of temporal involvement of specific phospholipases,
phospholipids, and possible endogenous mediators derived from arachidonic
acid-containing or other lipids.  Hyphal killing by PMN is a relatively
slow process, not attributable to the almost immediate lethal effects of
cell-free oxidants.  To define the mechanisms and loci of lethal hyphal
damage by PMN, a combined approach will employ both intact PMN and
granule-depleted cytoplast with added granule constituents separately or in
combination (e.g., myeloperoxidase, defensins, cathepsin G, lactoferrin,
lysozyme and elastase).  In addition to processes initiating PMN responses
to hyphae, we will begin to identify and study factors modulating the
sustained PMN activation response required for killing.  To define effects
of PMN on the target organisms, temporal biochemical and visual changes in
multiple localized fluorescent markers loaded into live hyphae will be
correlated with localized biochemical indicators of damage, PMN oxidant and
granule release, and their coincidence with the onset of killing.

## Key facts

- **NIH application ID:** 3126156
- **Project number:** 5R01AI015338-15
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CENTER HOSP
- **Principal Investigator:** RICHARD D DIAMOND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $360,702
- **Award type:** 5
- **Project period:** 1978-09-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126156

## Citation

> US National Institutes of Health, RePORTER application 3126156, PULMONARY AND SYSTEMIC KILLING OF OPPORTUNISTIC FUNGI (5R01AI015338-15). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126156. Licensed CC0.

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