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

Affiliations
  • 1Department of Oral Pathology, College of Dentistry, Kangnung National University, Gangneung, Korea. rchung@kangnung.ac.kr
  • 2Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University, Gangneung, Korea.
  • 3Department of Periodontology, College of Dentistry, Kangnung National University, Gangneung, Korea.
  • 4Department of Conservative Dentistry, College of Dentistry, Kangnung National University, Gangneung, Korea.
  • 5Mogam Biotechnology Research Institute, Yongin, Korea.

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
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