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.
Highlights
Neutrophil elastase is a protease that is involved in the tissue destruction and inflammation that characterize numerous diseases, including hereditary emphysema, chronic obstructive pulmonary disease, cystic fibrosis, adult respiratory distress syndrome, ischemic-reperfusion injury, rheumatoid arthritis, and periodontitis (Drugarin et al, 1998; Tremblay et al, 2003)
In the other m odel, the liner excisional cutaneous wound treated with fibrin sealant containing recombinant elastase inhibitor guamerin (rEIG) showed early wound constriction, lesser degree of inflam m atory cells influx, and com plete reepithelialization in 4-5 days, whereas the wound of control m ice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflam m atory cell infiltration, and consequencial form ation of greater granulation tissue at wound site
These data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating m ilieu of m icroorganism s in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PM Ns to inflam ed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflam m ation-generated proteases and the acute inflam m atory reaction
Summary
Neutrophil elastase is a protease that is involved in the tissue destruction and inflammation that characterize numerous diseases, including hereditary emphysema, chronic obstructive pulmonary disease, cystic fibrosis, adult respiratory distress syndrome, ischemic-reperfusion injury, rheumatoid arthritis, and periodontitis (Drugarin et al, 1998; Tremblay et al, 2003). Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with anti-microbial properties found in mucosal fluids It is expressed during cutaneous wound healing. In the SLPI-null mice, the impaired cutaneous wound healing with increased inflammation and elastase activity was observed suggesting that leukocyte protease inhibitor may play a pivotal role for optimal wound healing and the altered inflammatory profile involves enhanced activation of local TGF-β in SLPI-null mice (Ashcroft et al, 2000; Shin et al, 2003). The effect of a recombinant elastase inhibitor guamerin (rEIG) was analyzed in the animal wound models where degree of inflammation and exposure to infectious agents were significantly different. Paradoxical effect of rEIG on the healing of two different model wounds appeared a hindrance in the septic and an aid in aseptic conditions suggesting a possible multi-role(s) of elastase on the progression of inflammation at wound sites. K et al, 2000), was tested free of any endotoxin contamination
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
