# BIOCHEMICAL MECHANISMS OF IEN INDUCED MACROPHAGE TUMORIC

> **NIH NIH R01** · CLEVELAND CLINIC FOUNDATION · 1987 · $80,060

## Abstract

Participation of the mononuclear phagocyte system in defense against the
emergence and spread of cancer depends upon functional activation of its
elements, which requires the acquisition of requisite cellular and
biochemical capacities necessary for the execution of the tumoricidal
function.  Macrophage tumoricidal activation is acquired in discrete stages
induced by sequential exposure to specific signals present in the
extracellular environment.  Macrophage activating factor or
interferon-gamma (IFN-gamma) primes the macrophage for a subsequent
response triggered by a second signal such as lipopolysaccharide (LPS).
The biochemical mechanisms responsible for transducing these signals
represent potential regulatory points for therapeutic manipulation of
macrophage antitumor function.  However, these intracellular events remain
largely unidentified.

Treatment of responsive macrophage populations with physiologic doses of
IFN-gamma for as little as 2 to 4 hours resulted in a five-fold elevation
in the total cellular activity of the phospholipid, Ca++-dependent protein
kinase [protein kinase c (PKc)].  Furthermore, LPS treatment triggers a
series of unique protein phosphorylation events in macrophages.  These same
phosphorylations can be produced by stimulation with active phorbol
diesters suggesting that the protein kinase activity responsible for these
specific changes is PKc.

Both these findings lead to the hypothesis that IFN-gamma primes
macrophages by elevating PKc activity and that LPS triggers stimulation of
this enzyme, thus resulting in full activation. This hypothesis will be
tested by:  (1) identifying the structural and functional basis of the
elevation in PKc activity induced by treatment with interferon; (2)
determining the molecular basis whereby LPS stimulates the function of PKc;
and (3) characterizing the specific protein phosphorylation events induced
by both IFN-gamma and LPS.  (MB)

## Key facts

- **NIH application ID:** 3178831
- **Project number:** 7R01CA039621-04
- **Recipient organization:** CLEVELAND CLINIC FOUNDATION
- **SAM.gov UEI:** TDGUJ1WA4UJ9
- **Principal Investigator:** THOMAS A. HAMILTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $80,060
- **Award type:** 7
- **Project period:** 1987-05-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178831

## Citation

> US National Institutes of Health, RePORTER application 3178831, BIOCHEMICAL MECHANISMS OF IEN INDUCED MACROPHAGE TUMORIC (7R01CA039621-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178831. Licensed CC0.

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