Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury

Objectives: In lung ischemia-reperfusion injury, neutrophil migration from the vasculature to the interstitial spaces plays a major role in tissue inj ury. Degradation of the basement membrane, which is composed of extracellul ar matrix (ECM) molecules, is necessary for neutrophil migration. Matrix me talloproteinases (MMPs) might play a role in ECM degradation in lung ishemi a-reperfusion injury. We evaluated the changes in the activity of MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) gene expressio ns using rat lung transplantation models. Methods: We divided animals into 4 groups. Groups I and II served as contro l groups with intact lungs (Group I) and 24-hour cold-preserved lungs (Grou p II). Groups III and IV received lung grafts after 24-hour cold preservati on. The recipient animals were sacrificed 1 hour (Group III) or 24 hours (G roup IV) after transplantation. We evaluated lung injury histologically. We assessed MMP activity using zymography. We assessed MMP-2 MMP-9, and TIMP- 1 gene expression using biplex reverse transcriptase-polymerase chain react ion method. Results: In Groups III and IV, we noted severe ischemia-reperfusion injury. We noted no significant difference in enzyme activity and gene expression of MMP-2 between Groups I and IV. The MMP-9 activity and gene expression we re low during ischemia and increased on reperfusion. TIMP-1 gene expression was low during ischemia and at the early phase of reperfusion, and showed a dramatic increase at the late phase of reperfusion. Conclusions: Matrix metalloproteinase 9, but not MMP-2, may play an importa nt role in ischemia-reperfusion injury. TIMP-1 increases at the late phase of reperfusion and may compensate for the activity of MMP-9.