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Research article2010Peer reviewedOpen access

The inflammatory response following an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5

Younan George, Suber Freeman, Xing Wei, Shi Tong, Kunori Yuichi, Abrink Magnus, Pejler Gunnar, Schlenner Susan M., Rodewald Hans-Reimer, Moore Francis D. Jr., Stevens Richard L., Adachi Roberto, Austen K. Frank, Gurish Michael F.

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. The Journal of Immunology, 2010, 185: 7681-7690.

Published in

Journal of Immunology
2010, Volume: 185, number: 12, pages: 7681-7690
Publisher: American Association of Immunologists

      Associated SLU-program

      Future Animal Health and Welfare (until Jan 2017)

      UKÄ Subject classification

      Immunology

      Publication identifier

      DOI: https://doi.org/10.4049/jimmunol.1002803

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/31832