# MECHANISM OF MACROPHAGE DIVERSITY

> **NIH NIH R01** · EAST CAROLINA UNIVERSITY · 1993 · $117,723

## Abstract

This is a revised proposal to extend ongoing studies on regulation
of phenotypic expression in mononuclear phagocytes, a heterogeneous
but important component of the immune system.  The bone seeking
isotope 89Sr, is used to create bone marrow (BM) deprived monocyte-
depleted mice for the study of tissue macrophage functions.  Such
mice rapidly lose the capacity to express an immunosuppressive
prostaglandin-secreting splenic Mphi (PGSM) induced by the
immunomodulator, C. parvum.  Eicosanoid metabolism in peritoneal
Mphi, however, is unaffected by BM ablation.  We wish to determine
the origin of PGSM and the nature of regulatory influences of BM
and spleen on Mphi eicosanoid metabolism.  In addition, we wish to
investigate another aspect of Mphi activation and the effects of
enhanced IL-1 release on insulin release.

Specific aim (SA) 1.  To determine mechanisms regulating the
expression of PGSM by C. parvum and other Mphi activators.
Synthesis and release of eicosanoids by Mphi will be assessed by
RIA, HPLC and TLC in relation to BM and spleen cell interactions
in vivo and in vitro.  Populations will be defined by differential
radiosensitivity and selective shielding of BM and spleen.
Contributions of cell-bound and soluble factors will be studied in
vitro by incubating spleen and bone marrow cells from C. parvum
primed and unprimed mice either mixed or separated by microporous
filters.  Restoration of PGSM in vivo will be studied by
transfusions of BM from primed and unprimed donors into primed and
unprimed syngeneic recipients.  SA 2: To assess influences of
microenvironmental factors on PGSM expression with in vivo grafts
of primary BM stromal cells and the MC-1 stromal cell line in
conjunction with in vitro co-cultures of stromal cells and splenic
Mphi.  SA 3:  To determine the relationship of the Fcy1/y2b
receptor, phospholipase A2 activity and Ca++ in flux to PGSM
expression.  Expression of this receptor correlates with PGSM
activity following ip C. parvum in normal mice.  SA 4:  To
determine whether Mphi metabolism altered by activation results in
IL-modulation of insulin release.  The project should provide
useful information concerning environmental regulatory influences
on Mphi function relating to metabolism, inflammation and non-
specific aspects of immunologic activity.

## Key facts

- **NIH application ID:** 3127016
- **Project number:** 5R01AI017162-12
- **Recipient organization:** EAST CAROLINA UNIVERSITY
- **SAM.gov UEI:** HWPEKM8VFTJ9
- **Principal Investigator:** ALVIN VOLKMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $117,723
- **Award type:** 5
- **Project period:** 1988-12-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127016

## Citation

> US National Institutes of Health, RePORTER application 3127016, MECHANISM OF MACROPHAGE DIVERSITY (5R01AI017162-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127016. Licensed CC0.

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