Exp Mol Med.  2004 Jun;36(3):259-267.

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cut and exposed tongue wounds

• Lee SK
• Lee SS
• Song IS
• Kim YS
• Park YW
• Joo JY
• Um HS
• Kim JW
• Kim KY
• Choi SJ
• Jung KH
• Chung SI

Abstract

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.

Keyword

leukocyte elastase; mice; recombinant proteins; serine proteinase inhibitors; skin; tongue; wound healing

MeSH Terms

Animals
Enzyme Inhibitors/*pharmacology
Female
Fibrin Tissue Adhesive/pharmacology
Invertebrate Hormones/analysis/pharmacokinetics/*pharmacology
Leukocyte Elastase/*antagonists & inhibitors
Macrophages/immunology
Mice
Research Support, Non-U.S. Gov't
Skin/drug effects/*injuries/pathology
Tongue/drug effects/*injuries/pathology
Wound Healing/*drug effects