# ENDOTOXIN ACTIVATION OF MACROPHAGES ROLE OF GANGLIOSIDES

> **NIH NIH R01** · YALE UNIVERSITY · 1988 · $136,659

## Abstract

Gangliosides are ubiquitous components of eukaryotic plasma membranes.
They may function as receptors for bacterial toxins, peptide hormones,
viruses, and immunomodulatory agents (interferon, MIF).  A complex and
unique pattern of gangliosides is associated with lymphoid tissue.  More
than twenty new gangliosides appear when murine macrophages are activated
by endotoxin or other activating agents.  The physiologic role of these new
gangliosides is totally unknown.  Endotoxins interact with macrophages and
trigger a variety of biochemical responses many of which clearly play a
role in host defenses.  The molecular mechanisms by which endotoxins act on
macrophages are totally unknown.  The long term goal of this application is
to elucidate the mechanisms by which endotoxins interact with macrophages.
Specific attention will be paid to macrophage gangliosides as potentially
critical components of the plasma membrane which may be involved in the
transduction of activating signals.  This application proposes to determine
whether activating agents, both endogenous and exogenous, interact with
gangliosides from mononuclear phagocytes; to assess the expression of
specific gangliosides in different macrophage populations using monoclonal
antibodies directed against specific gangliosides; and to transfer
gangliosides between cell populations and assess whether new functions may
be acquired by the altered macrophages.  A two-dimensional TLC system has
been developed in our laboratory to display gangliosides purified from
lymphoid cells.  Monoclonal antibodies will be prepared using
endotoxin-ganglioside complexes as immunogens and a solid phase immunoassay
to detect positive clones.  These antibodies will be used in direct binding
assays on TLC plates to identify specific compounds.  In similar fashion,
the binding of bacterial endotoxins and gamma interferon to macrophage
gangliosides will be assessed.  The physiologic significance of a
particular ganglioside composition will be assessed using fusogenic
liposomes to transfer the gangliosides between populations of macrophages.
Phagocytosis and assays of oxidative metabolism will be used to assess
macrophage function.  These experiments will further define the molecular
basis of endotoxin-induced cellular responses.  Furthermore they will help
elucidate the significance of macrophage gangliosides as potential
receptors for immunomodulatory agents.

## Key facts

- **NIH application ID:** 3127689
- **Project number:** 5R01AI018099-06
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** JOHN L RYAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $136,659
- **Award type:** 5
- **Project period:** 1982-04-01 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127689

## Citation

> US National Institutes of Health, RePORTER application 3127689, ENDOTOXIN ACTIVATION OF MACROPHAGES ROLE OF GANGLIOSIDES (5R01AI018099-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127689. Licensed CC0.

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