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

R.A. Matthijsen, D. Huugen, N.T. Hoebers, B. de Vries, C.J. Peutz-Kootstra, Y. Aratani, M.R. Daha, J.W. Tervaert, W.A. Buurman, P. Heeringa

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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.
Original languageEnglish
Pages (from-to)1743-1752
JournalAmerican Journal of Pathology
Volume171
Issue number6
DOIs
Publication statusPublished - 1 Jan 2007

Cite this

Matthijsen, R.A. ; Huugen, D. ; Hoebers, N.T. ; de Vries, B. ; Peutz-Kootstra, C.J. ; Aratani, Y. ; Daha, M.R. ; Tervaert, J.W. ; Buurman, W.A. ; Heeringa, P. / Myeloperoxidase Is Critically Involved in the Induction of Organ Damage after Renal Ischemia Reperfusion. In: American Journal of Pathology. 2007 ; Vol. 171, No. 6. pp. 1743-1752.
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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.",
author = "R.A. Matthijsen and D. Huugen and N.T. Hoebers and {de Vries}, B. and C.J. Peutz-Kootstra and Y. Aratani and M.R. Daha and J.W. Tervaert and W.A. Buurman and P. Heeringa",
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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.; Buurman, W.A.; Heeringa, P.

In: American Journal of Pathology, Vol. 171, No. 6, 01.01.2007, p. 1743-1752.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Myeloperoxidase Is Critically Involved in the Induction of Organ Damage after Renal Ischemia Reperfusion

AU - Matthijsen, R.A.

AU - Huugen, D.

AU - Hoebers, N.T.

AU - de Vries, B.

AU - Peutz-Kootstra, C.J.

AU - Aratani, Y.

AU - Daha, M.R.

AU - Tervaert, J.W.

AU - Buurman, W.A.

AU - Heeringa, P.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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.

AB - 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.

U2 - 10.2353/ajpath.2007.070184

DO - 10.2353/ajpath.2007.070184

M3 - Article

VL - 171

SP - 1743

EP - 1752

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 6

ER -