Abstract | BACKGROUND: METHODS: RESULTS:
Ischemia-reperfusion injury induced growth-related oncogene/CINC-1-dependent neutrophil influx, and up-regulated tumor necrosis factor-alpha. MMP2 and MMP9, induced at 4 and 24 hr after IRI, respectively, were associated with detection of antigenic col(V) in bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-alpha; abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the donor before lung harvest and in the recipient after lung transplantation resulted in improved oxygenation and diminished polymorphonuclear leukocyte influx into the isograft. CONCLUSION:
MMP inhibition may be a potential therapy to prevent release of antigenic col(V) and ameliorate IRI in the transplant recipient.
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Authors | Takekazu Iwata, Masako Chiyo, Shigetoshi Yoshida, Gerald N Smith Jr, Elizabeth A Mickler, Robert Presson Jr, Amanda J Fisher, David D Brand, Oscar W Cummings, David S Wilkes |
Journal | Transplantation
(Transplantation)
Vol. 85
Issue 3
Pg. 417-26
(Feb 15 2008)
ISSN: 0041-1337 [Print] United States |
PMID | 18322435
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Collagen Type V
- Oncogene Proteins
- Tumor Necrosis Factor-alpha
- Metalloproteases
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Topics |
- Animals
- Chemotaxis, Leukocyte
- Collagen Type V
(metabolism)
- Down-Regulation
- Lung Transplantation
- Metalloproteases
(antagonists & inhibitors, metabolism)
- Neutrophils
(cytology)
- Oncogene Proteins
(metabolism)
- Rats
- Rats, Inbred WKY
- Reperfusion Injury
(metabolism, pathology, surgery)
- Tumor Necrosis Factor-alpha
(metabolism)
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