# MOLECULAR PATHOLOGY OF LPS INDUCED INJURY

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1992 · $387,693

## Abstract

The long term goal for our research is to understand bacterial
lipopolysaccharide (LPS) action at the molecular level. We will focus our
efforts on models that should help us understand how LPS induces cellular
injury during endotoxemia resulting from gram-negative bacillary
infections. We hypothesize that a significant contribution to the initial
host response to LPS is described by three sequential events; FIRST, the
formation of a complex between LPS and a plasma protein we discovered,
characterized and named LPS-binding protein (LBP). SECOND, the binding of
LPS-LBP complexes to monocytes/macrophages via a unique plasma membrane
receptor we have identified as CD14. THIRD, stimulation of macrophages by
LPS to rapidly release mediators such as TNF. To test this hypothesis we
will prepare monoclonal antibodies to LBP and CD14 for initial use in two
types of in vitro experiments; (i). to investigate their ability to block
binding of LPS to LBP and of LPS-LBP to CD14 on macrophages, (ii). to
identify the structures of LBP involved in LPS binding and binding of
LPS-LBP complexes to CD14. This latter approach will provide the requisite
data for design of polypeptides to be tested as inhibitors of LPS/LBP/CD14
interactions. To further test our hypothesis we will use a rabbit model of
endotoxic shock that approximates pathophysiologic changes in man during
endotoxemia to test whether antibodies and/or polypeptides shown to inhibit
LPS/LBP/CD14 interactions in vitro will modify LPS-induced release of TNF,
DIC and lethality. Implicit in these studies is the potential for
development of new therapeutic modalities to intervene in endotoxemia in
man.

## Key facts

- **NIH application ID:** 3126036
- **Project number:** 7R01AI015136-14
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** Richard J Ulevitch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $387,693
- **Award type:** 7
- **Project period:** 1978-08-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126036

## Citation

> US National Institutes of Health, RePORTER application 3126036, MOLECULAR PATHOLOGY OF LPS INDUCED INJURY (7R01AI015136-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126036. Licensed CC0.

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