Blockade of mast cell activation reduces cutaneous scar formation.
Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound.
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Lin
L
Chen
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Megan E
ME
Schrementi
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Matthew J
MJ
Ranzer
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Traci A
TA
Wilgus
Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Luisa A
LA
DiPietro
D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D015153:Blotting, Western; D002452:Cell Count; D002478:Cells, Cultured; D002921:Cicatrix / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D004205:Cromolyn Sodium / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000737:chemistry; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D009195:Peroxidase / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000293:injuries / Q000648:ultrastructure; D013194:Staining and Labeling / Q000379:methods; D053802:Tryptases / Q000276:immunology / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
D000199:Actins; D001391:Azo Compounds; D016207:Cytokines; C009798:C.I. direct red 80; D003094:Collagen; D009195:Peroxidase; D053802:Tryptases; D004205:Cromolyn Sodium