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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 12 (2004), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The release of mast cell granules is commonly associated with inflammation and fibrosis. However, does direct communication between mast cells and fibroblasts through gap junction intercellular communication (GJIC) occur? Fibroblast populated collagen lattice (FPCL) cast with mast cells show enhanced lattice contraction. Do released granules or GJIC between mast cells and fibroblasts promote enhanced lattice contraction? Mast cells preloaded with a fluorescent dye that readily passes through gap junctions were cast in FPCL. Dye passed from mast cells into fibroblasts within these cocultured mast cell-FPCLs. Fatty acid amide hydrolase inhibitor blocks the breakdown of oleamide, which is a potent endogenous inhibitor of GJIC. GJIC was blocked for 3 days when mast cells were pulsed for 3 hours with fatty acid amide hydrolase inhibitor. Mast cells pretreated with fatty acid amide hydrolase inhibitor cast in cocultured mast cell-FPCLs failed to enhance cocultured lattice contraction. Mast cell-FPCLs made with mouse fibroblasts unable to generate GJIC failed to show enhanced lattice contraction. Degranulated mast cells were equal to intact mast cells at enhancing cocultured mast cell-FPCL contraction. The supernatant from degranulated mast cells had no effect upon FPCL contraction. Therefore, enhanced mast cell-FPCL contraction appears to be independent of mast cell granules, but dependent upon GJIC between fibroblasts and mast cells. We speculate that mast cell–fibroblast GJIC may play a role in fibrosis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Wound healing requires fibroblast migration, synthesis of new extracellular matrix, and organization of that matrix, all of which depend upon myosin ATPase activation and subsequent cytoplasmic actin-myosin contraction. Myosin ATPase activity is optimized by phosphorylation of myosin light chain at serine 19. Several different signaling pathways can perform that phosphorylation, the focus here is calcium saturated calmodulin dependent -myosin light chain kinase (CaM-MLCK). It is proposed that CaM-MLCK phosphorylation of myosin light chain and subsequent myosin ATPase activation affects granulation tissue fibroblast behavior and contributes to wound contraction. Myosin ATPase activity generates actin-myosin contraction within fibroblasts. Myosin ATPase activity is involved in ATP-induced cell contraction, the generation of focal adhesions, fibroblast migration, fibroblast populated collagen lattice (FPCL) contraction, and wound contraction. The MLCK inhibitors ML-9 and ML-7 inhibited ATP-induced cell contraction, fibroblast migration, FA formation, and FPCL contraction. The calmodulin inhibitors W7 and fluphenazine blocked rat open wound contraction. In addition, fluphenazine delayed re-epithelialization. These findings support the idea that fibroblast CaM-MLCK activity is essential for tissue repair. We speculate that inhibition of CaM-MLCK may reduce or prevent detrimental fibrotic contracture.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 11 (2003), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Systemic ingestion of vanadate, a nonspecific inhibitor of tyrosine phosphatases, doubles wound breaking strength, enhances the packing of collagen fibers, and prevents the appearance of myofibroblasts in granulation tissue. Will the local application of vanadate mimic the systemic effects? Pairs of polyvinyl alcohol sponges, each with a central reservoir and attached injection port, were subcutaneously implanted in rats. Daily, one implant received 0.2 ml of saline and the other received 0.2 ml of 0.03 mM vanadate in saline. On day 7, harvested sponges had equivalent wet weights. The vanadate-treated sponges had fibroblasts separated by connective tissue, with a more intense birefringence of the collagen fibers. Transmission electron microscopy showed collagen more uniformly packed in the vanadate treated sponges where collagen fibers were equally spaced and had equal diameters. By immunohistology, myofibroblasts, defined by the expression of α-smooth muscle actin within stress fibers, were absent in vanadate-treated granulation tissue. The expression of α-smooth muscle actin was restricted to smooth muscle cells of blood vessels. Controls had densely packed α-smooth muscle actin staining myofibroblasts, weak birefringence, and randomly spaced collagen fibers with irregular diameters. We conclude that the local application of vanadate prevents the appearance of myofibroblasts and optimizes the organization of collagen fibers in developing granulation tissue. (WOUND REP REG 2003;11:204–212)
    Type of Medium: Electronic Resource
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