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
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.