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Myeloperoxidase is critically involved in the induction of organ damage after renal ischemia reperfusion

Matthijsen, R. A., Huugen, D., Hoebers, N. T., De Vries, B., Peutz-Kootstra, C. J., Aratani, Y., Daha, M. R., Tervaert, J. W. C., Buurman, W. A. & Heeringa, P., Dec-2007, In : American Journal of Pathology. 171, 6, p. 1743-1752 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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

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.

Original languageEnglish
Pages (from-to)1743-1752
Number of pages10
JournalAmerican Journal of Pathology
Volume171
Issue number6
Publication statusPublished - Dec-2007

    Keywords

  • HUMAN POLYMORPHONUCLEAR LEUKOCYTES, TERMINAL COMPLEMENT COMPONENTS, MEMBRANE ATTACK COMPLEX, MANNOSE-BINDING LECTIN, NECROSIS-FACTOR-ALPHA, MYOCARDIAL-INFARCTION, ISCHEMIA/REPERFUSION INJURY, ENDOTHELIAL-CELLS, APOPTOSIS, NEUTROPHILS

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