# DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION

> **NIH NIH R01** · U.S.UNIFORMED SERVICES UNIV  HLTH SCIS · 1987 · $82,848

## Abstract

Analysis of the nature and sequence of cell-derived and environmental
signals for progressive development of the fully activated macrophage was
the long-term goal of our original proposal.  Significant progress has been
made towards the elucidation of this differentiative pathway.  this
progress is largely attributable to the recent availability of highly
purified and cloned cytokines which were used in conjunction with
macrophages derived from the endotoxim "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 to
analyze the control mechanisms which govern colony stimulating factor
(CSF)- and gamma interferon (IFN-y)-induced effects on macrophage
proliferation and differentiation.  We will also assess the role of these
cytokines in the activation of macrophages to kill Salmonella typhimurium
intracellularly or to produce inflammatory mediators, such as elastase or
collagenase.  In addition, we plan to utilize bone marrow-derived
macrophages from endotoxim "responder" and "nonresponder" mice to delineate
the role of cytokines in the acquisition or endotoxin sensitivity.  Lastly,
we propose to define the contribution of ancillary, serum-derived signals
in cytokine-induced differentiation by using a "defined, complete"
serum-free medium.

The characterization of the cytokines involved, as well as 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
beneficial or detrimental roles.  The ability to stimulate activation of
host 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 or periodontal disease.
Finally, an improved understanding of the relationships between the state
of macrophage activation and endotoxin sensitivity might provide insights
for successful treatment of septic shock or other complications of Gram
negative bacillary infections.

## Key facts

- **NIH application ID:** 3128228
- **Project number:** 5R01AI018797-06
- **Recipient organization:** U.S.UNIFORMED SERVICES UNIV  HLTH SCIS
- **SAM.gov UEI:** Z83LJK5NWBC1
- **Principal Investigator:** Stefanie N. Vogel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $82,848
- **Award type:** 5
- **Project period:** 1982-04-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128228

## Citation

> US National Institutes of Health, RePORTER application 3128228, DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION (5R01AI018797-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128228. Licensed CC0.

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