Abstract |
In this study the role of myeloperoxidase (MPO) in a murine (C57BL/6) model of ischemia and reperfusion (I/R)-induced renal failure was investigated. The renal function after I/R was analyzed in MPO-deficient (Mpo(-/-)) mice and compared with wild-type (WT) controls. A significant reduction in renal function loss (blood urea nitrogen) was observed after 24 hours of reperfusion of ischemically damaged kidneys in Mpo(-/-) mice compared with I/R WT controls (I/R Mpo(-/-) = 31.3 +/- 1.7 mmol/L versus I/R WT = 42.8 +/- 2.1 mmol/L, sham = 7.0 +/- 0.5 mmol/L; P = 0.003). The early reperfusion phase (2 hours of reperfusion) was characterized by a substantial increase in apoptosis and early complement activation, surprisingly similar in Mpo(-/-) and WT mice. Improved renal function in Mpo(-/-) mice after extended reperfusion was accompanied by a reduced neutrophil influx (P = 0.017) compared with WT controls. Activation and deposition of complement was not significantly reduced in Mpo(-/-) mice compared with WT controls after 24 hours of reperfusion, indicating no specific in vivo role for MPO in activating complement after renal I/R. Taken together, these results demonstrated an important contribution of MPO in the induction of organ damage after renal I/R by influencing critical factors such as neutrophil extravasation but not complement activation.
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Authors | Robert A Matthijsen, Dennis Huugen, Nicole T Hoebers, Bart de Vries, Carine J Peutz-Kootstra, Yasuaki Aratani, Mohamed R Daha, Jan Willem Cohen Tervaert, Wim A Buurman, Peter Heeringa |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 171
Issue 6
Pg. 1743-52
(Dec 2007)
ISSN: 0002-9440 [Print] United States |
PMID | 18055546
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Apoptosis
(genetics)
- Complement Activation
(genetics)
- Kidney Diseases
(enzymology, immunology, pathology)
- Mice
- Mice, Mutant Strains
- Neutrophils
(immunology)
- Peroxidase
(genetics, physiology)
- Reperfusion Injury
(enzymology, immunology, pathology)
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