The long term goals of this proposal are: 1) to elucidate the mechanisms and the regulation of the fusion of mononuclear phagocytes (MNP) leading to the formation of both osteoclasts and giant cells. 2) to characterize the functional consequences of multinucleation in both normal and pathological bone resorption and in the host defense mechanisms involved in inflammatory reactions and tumors. The strategy adopted to reach these goals is based on the simultaneous use of two approaches which complement each other: 1) the first approach focuses upon the cellular and molecular basis for the particular tendency of cells of the MNP lineage to form polykaryons. This approach will more specifically involve the detection, the characterization and the kinetic analysis of new plasma membrane and soluble antigens. 2) the second approach focuses upon the role of the local microenvironment in the induction and the regulation of the fusion mechanism of the mononuclear precursors (MNP). Both agonist and antagonist factors will be searched for and analyzed. These two approaches closely interact in that the effects of local factors on the plasma membrane protein composition will also be studied. Parallel studies will be continued on in vivo induced osteoclasts and giant cells analyzing and comparing their respective antigenic determinants using immunoelectron microscopy techniques. In the long run, these studies may be of critical importance in the understanding of the functional implications of macrophage fusion is bone resorption and host defense mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035004-05
Application #
3157010
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1984-12-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Vignery, A; Raymond, M J; Qian, H Y et al. (1991) Multinucleated rat alveolar macrophages express functional receptors for calcitonin. Am J Physiol 261:F1026-32
Vignery, A; Niven-Fairchild, T; Ingbar, D H et al. (1989) Polarized distribution of Na+,K+-ATPase in giant cells elicited in vivo and in vitro. J Histochem Cytochem 37:1265-71