In healing and scarring the contractile process plays a significant role. In burn patients, scar contracture is a major contributor to morbidity. Mesenchymal cells usually fibroblasts produce the contractile force. A better understanding is needed of the morphological dynamics of forces generated by these cells for the eventual modulation of scar contracture. A 3 dimensional model composed of cultured fibroblasts suspended in a collagen matrix with serum containing culture medium is one method utilized to evaluate the contractile process. This fibroblast populated collagen lattice, FPCL, undergoes a reduction in size referred to as lattice contraction. Two other more simple in vitro models of the contractile process are the Cell Contraction model where the functioning of the cytoskeletal microfilament apparatus can be manipulated and the Thin-film Wrinkling model where the cytoplasmic components of cell movement can be followed under dynamic conditions. A number of purified cytoskeletal proteins, (actin, alpha-actinin and vinculin) are labeled with fluorescent tag and microinjected into cells prior to there introduction into one of our in vitro models. The location of these tagged proteins in fibroblasts may point to specific importance each has in the contractile process. In addition, the finding that type III collagen FPCL contract more than FPCL made with type I collagen suggest that the collagen matrix of scar may control the contractile process. The importance of some inflammatory cell products such as IL-1 from macrophages and lymphokines isolated from lymphocytes grown out from hypertrophic scars will be studied in terms of influencing collagen synthesis and the contractile process. Another approach to constrain this process is to limit connective tissue deposition. A combination of cortisone and oral heparin will be tried to modify neovascularization. Reducing neovascularization of wounds should reduce the amount of new connective tissue deposited which should affect the contractile process.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032705-06
Application #
3281770
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-12-01
Project End
1993-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Choi, M; Rabb, H; Arnaout, M A et al. (1995) Preventing the infiltration of leukocytes by monoclonal antibody blocks the development of progressive ischemia in rat burns. Plast Reconstr Surg 96:1177-85;discussion 1186-7
Choi, M; Ehrlich, H P (1993) U75412E, a lazaroid, prevents progressive burn ischemia in a rat burn model. Am J Pathol 142:519-28
Rittenberg, T; Ehrlich, H P (1992) Free fatty acids and dialyzed serum alterations of fibroblast populated collagen lattice contraction. Tissue Cell 24:243-51
Ehrlich, H P; Rockwell, W B; Cornwell, T L et al. (1991) Demonstration of a direct role for myosin light chain kinase in fibroblast-populated collagen lattice contraction. J Cell Physiol 146:1-7
Rockwell, W B; Ehrlich, H P (1991) An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells. Exp Mol Pathol 54:1-9
Rittenberg, T; Burd, D A; Ehrlich, H P (1990) Soluble factor(s) in rat wound fluid inhibit fibroblast populated lattice contraction. Exp Mol Pathol 52:132-40
Ehrlich, H P; Rajaratnam, J B (1990) Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. Tissue Cell 22:407-17
Hatz, R A; Kelley, S F; Ehrlich, H P (1989) The tetrachlorodecaoxygen complex reverses the effect of cortisone on wound healing. Plast Reconstr Surg 84:953-9
Ehrlich, H P (1988) The modulation of contraction of fibroblast populated collagen lattices by types I, II, and III collagen. Tissue Cell 20:47-50
Wyler, D J; Ehrlich, H P; Postlethwaite, A E et al. (1987) Fibroblast stimulation in schistosomiasis. VII. Egg granulomas secrete factors that stimulate collagen and fibronectin synthesis. J Immunol 138:1581-6

Showing the most recent 10 out of 15 publications