Abstract

We propose to isolate selected Connective Tissue Activating Peptides (CTAPs), and to define their chemical characteristics at a molecular level. Immunologic methods will be used to identify, localize and quantitate relevant human CTAPs in biological samples. Knowledge of the mechanisms of action of this class of regulators of connective tissue metabolism will be extended by identifying factors controlling synthesis and release of CTAPs, by defining the events occurring at the time of mediator-cell interaction, and by elucidating early consequences of activation (altered transport) as well as late events (glycosaminoglycan and proteoglycan synthesis). Relevance to rheumatic disease in man will be defined by studies of distribution and concentration of CTAPs in normal individuals and rheumatic patients, as well as by testing the therepeutic potential of selected agonists. Further, the activated human cell culture system will continue to be used as a model to test agents with potential for interdicting the inflammatory process. Our long-term objective is to sufficiently understand the mechanisms regulating connective tissue metabolism in normal man, and in degenerative and inflammatory processes, so that intelligent definitive intervention may become possible in rheumatic diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR010728-21
Application #
3154723
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1978-02-01
Project End
1988-06-30
Budget Start
1987-02-01
Budget End
1988-06-30
Support Year
21
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Castor, C William; Kotlyar, Alina; Edwards, Brian E (2002) Connective tissue activation XXXVIII: heparin/heparanase activity of human platelets resides in a high molecular weight protein, not in connective tissue activating peptide III. J Rheumatol 29:2337-44
Castor, C W; Smith, E M; Bignall, M C et al. (1997) Connective tissue activation. XXXVII. Effects of cytokine combinations, implications for an integrated cytokine network. J Rheumatol 24:2080-9
Cabral, A R; Castor, C W (1996) Connective tissue activating peptide-V and CD59: a molecule in search of a job. J Rheumatol 23:1126-9
Castor, C W; Andrews, P C; Swartz, R D et al. (1993) Connective tissue activation. XXXVI. The origin, variety, distribution, and biologic fate of connective tissue activating peptide-III isoforms: characteristics in patients with rheumatic, renal, and arterial disease. Arthritis Rheum 36:1142-53
Castor, C W; Smith, E M; Hossler, P A et al. (1992) Connective tissue activation. XXXV. Detection of connective tissue activating peptide-III isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture. Arthritis Rheum 35:783-93
Tai, P K; Liao, J F; Hossler, P A et al. (1992) Regulation of glucose transporters by connective tissue activating peptide-III isoforms. J Biol Chem 267:19579-86
Castor, C W; Smith, E M; Bignall, M C et al. (1991) Preparation and bioassay of connective tissue activating peptide III and its isoforms. Methods Enzymol 198:405-16
Castor, C W; Walz, D A; Johnson, P H et al. (1990) Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. J Lab Clin Med 116:516-26
Sisson, T H; Castor, C W (1990) An improved method for immobilizing IgG antibodies on protein A-agarose. J Immunol Methods 127:215-20
Castor, C W; Walz, D A; Ragsdale, C G et al. (1989) Connective tissue activation. XXXIII. Biologically active cleavage products of CTAP-III from human platelets. Biochem Biophys Res Commun 163:1071-8

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