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Mactinin treatment promotes wound‐healing‐associated inflammation in urokinase knockout mice
Author(s) -
Luikart Sharon D.,
LevayYoung Brett,
Hinkel Tim,
Shearer Jeffry,
Mills Charles,
Caldwell Michael D.,
Gyetko Margaret R.,
Oegema Theodore R.
Publication year - 2006
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1743-6109.2006.00101.x
Subject(s) - knockout mouse , wound healing , urokinase , inflammation , proinflammatory cytokine , hydroxyproline , immunology , monocyte , granulation tissue , chemistry , biology , medicine , receptor , biochemistry
Mactinin, a 31 kDa fragment from the amino‐terminal end of α‐actinin, is chemotactic for monocytes and can promote monocyte/macrophage maturation. Macrophages are essential for wound healing, in which they play key roles in debridement, angiogenesis, fibroblast proliferation, and collagen metabolism. We have previously determined that urokinase is necessary to form mactinin from extracellular α‐actinin, which may be present at sites of inflammation as a result of cell movement. Thus, urokinase knockout mice are unable to form mactinin and therefore are an ideal model to study mactinin's effects on wound healing. Saline‐ and mactinin‐treated wounds were analyzed in a subcutaneous sponge wound model in both wild‐type and urokinase knockout mice. The wounded urokinase knockout mice had markedly decreased leukocyte infiltration compared with wounded wild‐type mice. In addition, production of the proinflammatory cytokine, interleukin‐12, and of collagen was also decreased in knockouts. Treatment of knockout mice with mactinin resulted in leukocyte infiltration numbers, interleukin‐12 levels, and hydroxyproline measurements similar to those in wild‐type mice. The results suggest that impaired wound healing in urokinase‐deficient mice can be restored by administration of mactinin.