Published online before print November 30, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070184

Accepted for publication August 30, 2007.

Article

Myeloperoxidase Is Critically Involved in the Induction of Organ Damage after Renal Ischemia Reperfusion

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^*@, and Peter Heeringa

From the Department of General Surgery, *Nutrition, and Toxicology, Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; the Departments of Immunology and Pathology, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht, Maastricht, The Netherlands; the Department of Nephrology,^¶ Leiden University Medical Center, Leiden, The Netherlands; and the Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City University, Yokohama, Japan

^@ To whom correspondence should be addressed. E-mail: w.buurman{at}ah.unimaas.nl.

	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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