This project will explore an experimental model of scleroderma in the mouse. The model is based on (a) the probable involvement of autoimmune immunopathologic processes in idiopathic scleroderma, and (b) the production of a scleroderma-like illness in human graft-versus-host disease (GVHD), as well as in chronic GVHD in rodents. We plan to define the requirements for establishing and boosting a chronic GVHD in mice across various histocompatibility barriers. We will follow skin histopathology and autoimmune antibodies, and will study the role of the thymus and of cyclophosphamide on GVHD. The modulation of skin changes, including fibronectin deposition, and the effects of bleomycin will be measured. These studies should provide insight into the nature of the changes found in idiopathic scleroderma (progressive systemic sclerosis) and on the tissue injury seen in chronic GVHD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR031220-06
Application #
3156002
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1982-07-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Claman, H N; Spiegelberg, H L (1990) Immunoglobulin dysregulation in murine graft-vs-host disease: a hyper-IgE syndrome. Clin Immunol Immunopathol 56:46-53
Holda, J H; Maier, T; Claman, H N (1990) IL-3, IL-4, and IL-6 enhance IFN-gamma-dependent bone marrow natural suppressor activity. Cell Immunol 125:459-68
Levi-Schaffer, F; Mekori, Y A; Segal, V et al. (1990) Histamine release from mouse and rat mast cells cultured with supernatants from chronic murine graft-vs-host splenocytes. Cell Immunol 127:146-58
Claman, H N (1989) On scleroderma. Mast cells, endothelial cells, and fibroblasts. JAMA 262:1206-9
Maier, T; Holda, J H; Claman, H N (1989) Murine natural suppressor cells in the newborn, in bone marrow, and after cyclophosphamide. Genetic variations and dependence on IFN-gamma. J Immunol 143:491-8
Claman, H N; Holda, J H; Maier, T et al. (1988) Chronic graft-vs.-host disease: changes in natural suppressor cells and mast cells. Isr J Med Sci 24:367-9, 371
Choi, K L; Giorno, R; Claman, H N (1987) Cutaneous mast cell depletion and recovery in murine graft-vs-host disease. J Immunol 138:4093-101
Giorno, R; Choi, K L; Claman, H N (1987) Simultaneous in situ detection of IgE receptors and cytoplasmic granules in murine cutaneous mast cells. J Immunol Methods 99:163-6