# DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION

> **NIH NIH R01** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 1990 · $211,721

## Abstract

Analysis of the nature and sequence of cell-derived and
environmental signals required for the development of the fully
activated macrophage was the long-term goal of our original
proposal.  Significant progress has been made towards the
elucidation of the cellular and molecular mechanisms which
control the acquisition of specific cell surface markers and
functions during macrophage development.  This progress is
largely attributable to the recent availability of highly
purified and cloned cytokines (such as recombinant Colony
Stimulating Factors and interferons) which were used in
conjunction with macrophages derived from the endotoxin
"hyporesponsive" C3H/HeJ mouse strain.  In the studies described
herein, we will continue to utilize this extremely sensitive
system to extend our original findings.  We propose (1) to
examine the potential role of two distinct species of colony
stimulating factor, i.e., CSF-1 and GM-CSF, in the generation of
macrophage heterogeneity; (ii) to analyze further the molecular
mechanisms which underlie the induction and down-regulation of
macrophage Fc receptor and Ia antigen expression, as well as
modulation of the glucocorticoid receptor; (iii) to examine the
differentiation signals which may underlie acquisition of
endotoxin sensitivity in vivo and in vitro; (iv) to examine the
role of macrophage-derived interferon in macrophage
differentiation; (v) to define the intracellular signals required
for the acquisition of different stages of cytokine-induced
macrophage differentiation; and (vi) to assess the capacity of a
unique cytokine fusion protein to induce macrophage
differentiation.

The characterization of the cytokines involved, as well as a
delineation of the specific sequences of intra- and intercellular
signals that result in the development of the fully activated
macrophage, could provide novel therapeutic approaches for
diseases in which activated macrophages have been shown to have
beneficial or detrimental roles.  The ability to stimulate
activation of hosts macrophages might benefit patients who have
neoplasms or infections with intracellular pathogens.  In
contrast, the capacity to control macrophage activation, such
that the production of toxic mediators is mitigated, may be
beneficial to patients who suffer from chronic inflammatory
diseases, such as rheumatoid arthritis, periodontal disease, or
inflammatory bowel disease.  Finally, an improved understanding
of the relationships between the state of macrophage activation
and endotoxin sensitivity might provide insights for the
successful treatment of septic shock or other complications of
Gram negative bacillary infections.

## Key facts

- **NIH application ID:** 3128226
- **Project number:** 2R01AI018797-08A1
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **SAM.gov UEI:** UYLKBRENAPG5
- **Principal Investigator:** Stefanie N. Vogel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $211,721
- **Award type:** 2
- **Project period:** 1982-04-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128226

## Citation

> US National Institutes of Health, RePORTER application 3128226, DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION (2R01AI018797-08A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128226. Licensed CC0.

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