TY - JOUR
T1 - The inflammatory response after an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5
AU - Younan, George
AU - Suber, Freeman
AU - Xing, Wei
AU - Shi, Tong
AU - Kunori, Yuichi
AU - Åbrink, Magnus
AU - Pejler, Gunnar
AU - Schlenner, Susan M.
AU - Rodewald, Hans Reimer
AU - Moore, Francis D.
AU - Stevens, Richard L.
AU - Adachi, Roberto
AU - Austen, K. Frank
AU - Gurish, Michael F.
PY - 2010/12/15
Y1 - 2010/12/15
N2 - 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-KitW/KitWν 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.
AB - 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-KitW/KitWν 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.
UR - http://www.scopus.com/inward/record.url?scp=78650634216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650634216&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1002803
DO - 10.4049/jimmunol.1002803
M3 - Article
C2 - 21076070
AN - SCOPUS:78650634216
SN - 0022-1767
VL - 185
SP - 7681
EP - 7690
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -