# Study the interaction between Lipopolysaccharide-Binding Protein and Immune Cell Membranes

> **NIH NIH R03** · TEXAS ENGINEERING EXPERIMENT STATION · 2020 · $74,250

## Abstract

Project Summary
 Dysregulated immune responses to lipopolysaccharide (LPS, endotoxin) can lead to many inflammatory
diseases. The innate immune system detects LPS through a series of pattern recognition receptors. One of the
key receptors, LPS-binding protein (LBP), recognizes LPS, disassembles LPS aggregates in extracellular fluids,
and then delivers LPS to the receptors on immune cell surfaces. It is documented that the appropriate
concentration of LBP can lead to over 1,000-fold enhancement of LPS-induced immune response. The recent
clinical study of endotoxemia suggested targeting LPS is a better strategy than antimicrobial therapy to reduce
mortality in multiple-trauma patients with septic shock. Therefore, the neutralization of LBP function leading to
the reduction of LPS-induced immune response becomes an attractive therapeutic approach. Prior in vivo and
in vitro studies show that inhibition of LBP could attenuate LPS-induced inflammation. However, lack of
fundamental knowledge of LBP is the main obstacle to the development of LBP-neutralization therapy. Prior
studies reported that delivery of LPS to immune cell surface is activated by the adsorption/intercalation of LBP
to cell membrane. The PIs propose to discover a set of cell membrane molecules involved in LBP adsorption;
thus, the assembly of these molecules can serve as a high LBP affinity reagent for endotoxin shock intervention.
LBP adsorption is determined by cooperative actions between multiple membrane molecules rather than a single
membrane molecule. In order to observe the synergistic effects of different membrane molecules, a new
Membrane Perturbation Method developed by the PIs will be applied. In brief, macrophage membranes will be
reconstituted onto the sensor surface and then perturbed by inserting the membrane molecules purified from
native macrophages. Because the reconstituted membrane preserves the molecules in native cell membranes,
the complex interplay between membrane molecules can be identified. To complete this complex analysis, large
data sets are required to survey many different experimental conditions. Thus, the PIs will use their unique
nanocube-based membrane array, which enables large-scale quantitative analysis of protein binding to cell
membrane surface. The high-throughput and easy-to-use features of this unique tool address these critically
needed aspects. After identifying the major molecules contributing to LBP-membrane adsorption, the PIs will
fabricate synthetic liposomes containing these high affinity molecules to attenuate LPS-induced inflammation in
RAW 264.7 murine macrophages. Pro- (TNF-, IL-1, IL-6) and anti-inflammatory cytokines (IL-10, IL-4) will be
measured to determine the LBP-neutralization efficiency. The efficacy of LPS detoxification will be quantified by
the rate of fluorescence conjugated LPS transport to synthetic liposomes. This preliminary study will provide a
new strategy for the intervention of LPS related inflammatory dise...

## Key facts

- **NIH application ID:** 9867621
- **Project number:** 5R03AI139650-02
- **Recipient organization:** TEXAS ENGINEERING EXPERIMENT STATION
- **Principal Investigator:** ARUL JAYARAMAN
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $74,250
- **Award type:** 5
- **Project period:** 2019-02-07 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867621

## Citation

> US National Institutes of Health, RePORTER application 9867621, Study the interaction between Lipopolysaccharide-Binding Protein and Immune Cell Membranes (5R03AI139650-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9867621. Licensed CC0.

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