# CANDIDA ADHERENCE & PENETRATION OF VASCULAR ENDOTHELIUM

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 1993 · $149,335

## Abstract

Candida are now the fourth most common organisms recovered from blood of
hospitalized patients and comprise 10% of the blood isolates.  Although
potent antifungals exist, mortality rates from candidal septicemia remain
nearly 50%.  Because of this unacceptably high death rate, we have
studied strategies for enhancing host defenses against Candida.  Using
monolayers of human vascular endothelial cells in vitro, we have examined
the mechanisms by which Candida adhere to endothelial cells and escape
from the vascular compartment to infect visceral organs.

During the past grant period, we found that Candida stimulates
endothelial cells to produce specific prostaglandin mediators of
inflammation (PGI2, PGF2alpha, PGE2) in vitro, by enhancing arachidonic
acid mobilization and synthesis of cyclooxygenase.  We found also that
INF-gamma induces endothelial cells to resist candidal damage.
Additionally, we characterized the human complement receptor (CR)-like
molecules on C. albicans further by defining their antigenic similarities
to the human CR2 and CR3.  We inhibited candidal adherence to endothelial
cells with candidal extracts containing these receptors, supporting their
role as adhesions.  Finally, we extracted a cationic peptide from
platelets that has potent anti-candidal activity and may be important in
host defense against Candida.

Since adherence is the first step in endothelial cell invasion, we intend
to clone the adherence genes of Candida in Saccharomyces cerevisiae and
transform non-adherent Saccharomyces into adherent strains.  From these
DNA transformation studies, the gene product/s responsible for adherence
of Candida can be identified and strategies for blocking adherence
developed.  To devise strategies to improve host defenses against
Candida, we will investigate how INF-gamma induces endothelial cells to
resist candidal damage and we will determine whether GM-CSF, and IL1-beta
have direct protective effects on endothelial cells.  We will develop
strategies to increase the combined capacity of neutrophils and
endothelial cells to kill Candida by priming both cell types with the
immunomodulators INF-gamma, GM-CSF, and IL-1beta.  Additionally, we will
elucidate the mechanisms by which activated neutrophils may induce
cytoprotective responses in endothelial cells.

## Key facts

- **NIH application ID:** 3129445
- **Project number:** 2R01AI019990-09
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **SAM.gov UEI:** LTJVF4QSFCP9
- **Principal Investigator:** John E Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $149,335
- **Award type:** 2
- **Project period:** 1984-09-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129445

## Citation

> US National Institutes of Health, RePORTER application 3129445, CANDIDA ADHERENCE & PENETRATION OF VASCULAR ENDOTHELIUM (2R01AI019990-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129445. Licensed CC0.

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