Mactinin treatment promotes wound-healing-associated inflammation in urokinase knockout mice.
Mactinin, a 31 kDa fragment from the amino-terminal end of alpha-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 alpha-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.
Luikart
Sharon D
SD
Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA. Sharon.Luikart@MED.VA.GOV
Levay-Young
Brett
B
Hinkel
Tim
T
Shearer
Jeffry
J
Mills
Charles
C
Caldwell
Michael D
MD
Gyetko
Margaret R
MR
Oegema
Theodore R
TR
D000185:Actinin / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D010446:Peptide Fragments; C485291:mactinin, human; D000185:Actinin; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D006909:Hydroxyproline