Fibrin assembly and formation is related to fibroblast activity, a relationship of importance to wound healing and inflammation. To study this interaction, sophisticated, state-of-the-art physical measurements are required. The basic types of information necessary to characterize these interactions include mass/length ratios of fibrin fibers, diffusion coefficients of both fibrin intermediates and perturbing macromolecules, selective measurement of diffusion in the presence of other interfering macromolecules, of fibroblast and endothelial cells, and rheological assessment of modified fibrin gels. We have developed a variety of light scattering and rheological techniques to permit an orderly means to determine the influence of selected naturally occurring macromolecules, e.g. immunoglobulins, albumin, collagen, leukocyte lysosomal cationic protein, fibronectin, etc. on fibrin assembly. Plasmin digestion of fibrin gels formed with with specific structural characteristics will be studied by Holographic light scattering, HRS. In addition, new technology including the combination of electrophoretic light scattering (ELS) and HRS, has been developed to investigate the interaction of fibrin with fibroblasts and endothelial cells. Physical properties of fibrin receptors on fibroblast and endothelial cell surfaces will be studied by several different light scattering methods. Fibroblast function will be related to specific structural requirements of fibrin, namely fiber diameter, gel rigidity, fiber density and the presence of other macromolecules, e.g. fibronectin. This information will be highly useful in a variety of clinical settings related to host defense mechanisms, namely the inflammatory response and wound healing.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033865-02
Application #
3283997
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Gabriel, D A; Carr, M E; Cook, L et al. (1987) Spontaneous antithrombin in a patient with benign paraprotein. Am J Hematol 25:85-93
Carr Jr, M E; Gabriel, D A; McDonagh, J (1987) Influence of factor XIII and fibronectin on fiber size and density in thrombin-induced fibrin gels. J Lab Clin Med 110:747-52
Carr, M E; White 2nd, G C; Gabriel, D A (1987) Platelet factor 4 enhances fibrin fiber polymerization. Thromb Res 45:539-43
Carr Jr, M E; Gabriel, D A; Herion, J C et al. (1986) Granulocyte lysosomal cationic protein alters fibrin assembly: a possible mechanism for granulocyte control of clot structure. J Lab Clin Med 107:199-203
Carr Jr, M E; Gabriel, D A; McDonagh, J (1986) Influence of Ca2+ on the structure of reptilase-derived and thrombin-derived fibrin gels. Biochem J 239:513-6
Carr Jr, M E; Gabriel, D A (1986) Hyperfibrinogenemia as a cause of prolonged thrombin clotting time. South Med J 79:563-70
Arunyawongsakorn, U; Johnson Jr, C S; Gabriel, D A (1985) Tracer diffusion coefficients of proteins by means of holographic relaxation spectroscopy: application to bovine serum albumin. Anal Biochem 146:265-70