# PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1992 · $161,622

## Abstract

Normal enteric bacteria have been shown to seed inflammatory foci in
the peritoneal cavity by direct contamination through anatomically intact
bowel, thereby producing or perpetuating bacterial peritonitis.  Prior
work in this grant has shown that fluorescent latex beads as well as
bacteria will pass through the bowel wall to the serosa.  We have
provided evidence that particulate transport takes place within
macrophages which normally reside in the submucosa of the bowel.  We now
plan to employ isolated, perfused, mucosal/submucosal membranes in vitro
to investigate by what mechanisms inert particles (latex beads) or
bacteria (E. coli) pass through the intact epithelial layers of the
alimentary tract to reach the submucosa.
     The bowel wall will be split in a plane between the submucosa and
the circular muscle.  The mucosal/submucosal membrane will be mounted in
Ussing chambers permitting both sides of the membrane to be oxygenated
and perfused.  A stable potential difference indicates viability and a
stable resistance indicates electrochemical impermeability of the
membrane.  Labelled beads or bacteria introduced on the mucosal surface
pass through the epithelial membrane to the submucosal surface where they
can be quantitated by fluorescence and/or quantitative bacteriology.
Preliminary kinetic and microanatomical studies suggest that particulate
passage is an energy-dependent function of the living intestinal
epithelial cell which incorporates the particle and passes it through to
the lamina propria.  The proposed studies are designed to investigate the
microanatomical and functional details of this normal mechanism which
will be compared with gut from animals with infection and shock.
Furthermore, the importance of enteropathogenic virulence characteristics
and bacterial adherence will be assessed.  The role of intestinal mucus,
tight junctions, brush border glycocalyx, lamina propria, T cells,
various cytokines, and IgA on normal transepithelial passage of bacteria
will be tested.  Selected probes to evaluate the role of intraepithelial
pinocytosis, phagocytosis, and bacterial killing will be employed.
Considerable information should be gained on the mechanism by which the
intestinal flora gain entrance into the body under normal conditions and
during physiologic stress.

## Key facts

- **NIH application ID:** 3125617
- **Project number:** 5R01AI014032-14
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** RICHARD L. SIMMONS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $161,622
- **Award type:** 5
- **Project period:** 1987-12-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125617

## Citation

> US National Institutes of Health, RePORTER application 3125617, PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS (5R01AI014032-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125617. Licensed CC0.

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