title: The inflammatory response after an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5.
abstract: A second-degree epidermal scald burn in mice elicits an inflammatory response mediated by natural IgM directed to nonmuscle myosin with complement activation that results in ulceration and scarring. We find that such burn injury is associated with early mast cell (MC) degranulation and is absent in WBB6F1-Kit(W)/Kit(Wv) mice, which lack MCs in a context of other defects due to a mutation of the Kit receptor. To address further an MC role, we used transgenic strains with normal lineage development and a deficiency in a specific secretory granule component. Mouse strains lacking the MC-restricted chymase, mouse MC protease (mMCP)-4, or elastase, mMCP-5, show decreased injury after a second-degree scald burn, whereas mice lacking the MC-restricted tryptases, mMCP-6 and mMCP-7, or MC-specific carboxypeptidase A3 activity are not protected. Histologic sections showed some disruption of the epidermis at the scald site in the protected strains suggesting the possibility of topical reconstitution of full injury. Topical application of recombinant mMCP-5 or human neutrophil elastase to the scalded area increases epidermal injury with subsequent ulceration and scarring, both clinically and morphologically, in mMCP-5-deficient mice. Restoration of injury requires that topical administration of recombinant mMCP-5 occurs within the first hour postburn. Importantly, topical application of human MC chymase restores burn injury to scalded mMCP-4-deficient mice but not to mMCP-5-deficient mice revealing nonredundant actions for these two MC proteases in a model of innate inflammatory injury with remodeling.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: George
authors.initials: G
authors.lastname: Younan
authors.forename: Freeman
authors.initials: F
authors.lastname: Suber
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Tong
authors.initials: T
authors.lastname: Shi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kunori
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schlenner
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.forename: Francis D
authors.initials: FD
authors.lastname: Moore
authors.forename: Richard L
authors.initials: RL
authors.lastname: Stevens
authors.forename: Roberto
authors.initials: R
authors.lastname: Adachi
authors.forename: K Frank
authors.initials: KF
authors.lastname: Austen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Gurish
mesh_terms: D000818:Animals; D002056:Burns / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D043422:Carboxypeptidases A / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D053818:Chymases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D002921:Cicatrix / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation; D019272:Leukocyte Elastase / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D018448:Models, Immunological; D009218:Myosins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D053802:Tryptases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007075:Immunoglobulin M; C509190:Tpsb2 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse; D012697:Serine Endopeptidases; C066932:mast cell protease 4; D019272:Leukocyte Elastase; C509226:CMA1 protein, human; D053818:Chymases; D053802:Tryptases; D009218:Myosins