# MOLECULAR MECHANISMS OF MACROPHAGE MULTINUCLEATION

> **NIH NIH R01** · YALE UNIVERSITY · 1993 · $218,293

## Abstract

Osteoclasts and multinucleated giant cells originate from the fusion
of mononuclear precursors of the monocyte-macrophage lineage.
Multinucleation is one of the main phenotypic characteristics of these
cells.  Although fusion is an essential step in formation of these
cells, the molecular mechanisms by which it occurs, and the functional
consequences of multinucleation are poorly understood.  Osteoclast and
giant cells share some similarities but are clearly distinct cell types
and reside in different microenvironments.  As far as their
similarities are concerned, we have shown that multinucleated alveolar
macrophages express, like osteoclasts, a high and polarized
concentration of plasma membrane Na,K-ATPases as well as a high copy
number of receptors for calcitonin.  Most importantly, it has been
recently demonstrated that alveolar macrophages, cultured under
appropriate conditions, are capable of resorbing bone in vitro.  In
this application we propose to use macrophages as a model system to
study the mechanism of fusion of cells of the monocyte- macrophage
lineage.

To investigate the mechanism of cell fusion, we hypothesize that the
formation of polykaryons must depend upon cell surface molecules
specific for monocyte-macrophages.

During the previous funding period, we have identified macrophage-
specific surface molecules which potentially mediate fusion.  We have
generated monoclonal antibodies selected for their ability to prevent
fusion of macrophages in vitro.  Preliminary biochemical character-
ization of one of the antigens has revealed a surface glycoprotein
which is specifically detected in macrophages at the time of their
fusion.  A glycoprotein of similar molecular weight is detected by
three additional monoclonal antibodies which we also selected for their
ability to prevent fusion.

The long-term goal of this project is to elucidate the fusion mechanism
of macrophages which leads to the formation of polykaryons.

The SPECIFIC AIMS of the present application are:

1.  To characterize at the molecular level the structure of the
antigens recognized by our monoclonal antibodies 12D6, 10B11, 10C4 and
10C5 which block macrophage fusion in vitro.  This will be accomplished
by cloning cDNAs coding for the corresponding antigens.

2.  To establish a suitable cell expression system for the functional
analysis of these antigens.

3.  To determine the role of 12D6 antigen in osteoclast and giant cell
formation in vivo, and the regulation of its expression by agents that
affect osteoclast differentiation.

## Key facts

- **NIH application ID:** 3157006
- **Project number:** 2R01AR035004-07A2
- **Recipient organization:** YALE UNIVERSITY
- **SAM.gov UEI:** FL6GV84CKN57
- **Principal Investigator:** Agnes Vignery
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $218,293
- **Award type:** 2
- **Project period:** 1984-12-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157006

## Citation

> US National Institutes of Health, RePORTER application 3157006, MOLECULAR MECHANISMS OF MACROPHAGE MULTINUCLEATION (2R01AR035004-07A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157006. Licensed CC0.

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