An important aspect both of healing and scarring is the contractile process which is a major component of the morbidity associated with the discharged burn patient. Mesenchymal cells, referred to here as fibroblasts, produce the contractile forces generated in the contractile process. To better study and understand these mechanisms, and to gain possible control of these forces, a three dimensional in vitro model system, the fibroblast populated collagen lattice (EPCL) is employed. Tissue cultured fibroblasts suspended in a collagen matrix actively reduce the size of that matrix in the process known as lattice contraction. Local increases in prostaglandins (PGE) may be produced either by directly adding PGE or by stimulating the fibroblast endogenous synthesis of PGE2, which inhibit lattice contraction. Characteristics of lattice contraction inhibition are a morphological inability of the incorporated fibroblasts to spread and elongate, since they remain spherical in shape; and a biochemical increase in intracellular cAMP concentrations. It is proposed that cAMP inhibits lattice contraction by inhibiting the functions of intracellular microfilaments. In particular, microfilaments do not form """"""""stress fibers"""""""" resulting fibroblasts which cannot spread and elongate. Other cytoskeletal components such as microtubules and plasma membranes may also be altered. The dynamics of the structural changes of microfilaments, microtubules and plasma membranes will be monitored by the use of a non-immuno fluorescence probe, NBD-phallacidin, or by intracellular micro injections of fluorescently labeled microfilaments, microtubules or plasma membrane structural proteins prior to fibroblast incorporation into FPCL. Relationships will be searched for relating cytoskeletal and contractile apparatus elements and for the mechanisms of the contractile force developed by fibroblasts. It is anticipated that information from these in vitro studies will produce new approaches to the ultimate control of the contractile processes associated with in vivo healing and/or scarring.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032705-02
Application #
3281767
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
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
Rockwell, W B; Ehrlich, H P (1991) An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells. Exp Mol Pathol 54:1-9
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
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

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