Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury

P. K. Chatterjee, K. Zacharowski, S. Cuzzocrea, Paul Anthony James Brown, Keith Nicol Stewart, H. Mota-Filipe, C. Thiemermann

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background. The aim of this study was to investigate whether in vivo administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus , protects the kidney against the renal dysfunction and injury caused by ischemia/reperfusion (I/R).

Methods. Male Wistar rats were administered LTA from S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were measured for the assessment of renal function, tubular and reperfusion-injury. Renal sections were used for histological grading of renal injury and for immunohistochemical localization of P-selectin, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Nitric oxide (NO) production was determined by measurement of plasma nitrite/nitrate levels.

Results. LTA pretreatment significantly reduced renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as well as histological evidence of renal injury. LTA also reduced the expression of P-selectin and kidney MPO activity associated with renal I/R. MDA levels were significantly reduced by LTA pretreatment suggesting a reduction in the lipid peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment also markedly reduced both the expression of iNOS and the formation of nitrotyrosine associated with renal I/R. Although LTA significantly reduced plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels remained at levels significantly higher than that measured from the plasma obtained from Sham-operated animals.

Conclusions. These data suggest, to our knowledge for the first time, that LTA pretreatment for 24 hours significantly reduces renal I/R injury. We propose that the mechanism of the protective effect involves reduction of the production of NO, ROS and peroxynitrite subsequent to reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA pretreatment resulted in a reduction of iNOS expression and NO production, we hypothesize that the remaining significant levels of NO contribute to the beneficial actions provided by LTA.

Original languageEnglish
Pages (from-to)1249-1263
Number of pages14
JournalKidney International
Volume62
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • kidney transplantation
  • reperfusion-injury
  • Gram positive bacteria
  • lipopolysaccharide
  • P-selectin
  • inducible nitric oxide synthase
  • nitric oxide
  • peroxynitrite
  • NITRIC-OXIDE SYNTHASE
  • ISCHEMIA-REPERFUSION INJURY
  • MONOPHOSPHORYL LIPID-A
  • CELL-ADHESION-MOLECULES
  • SMOOTH-MUSCLE CELLS
  • RAT-KIDNEY
  • PEROXYNITRITE FORMATION
  • MYOCARDIAL-ISCHEMIA
  • EPITHELIAL-CELLS
  • IN-VIVO

Cite this

Chatterjee, P. K., Zacharowski, K., Cuzzocrea, S., Brown, P. A. J., Stewart, K. N., Mota-Filipe, H., & Thiemermann, C. (2002). Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury. Kidney International, 62(4), 1249-1263. https://doi.org/10.1111/j.1523-1755.2002.kid580.x

Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury. / Chatterjee, P. K.; Zacharowski, K.; Cuzzocrea, S.; Brown, Paul Anthony James; Stewart, Keith Nicol; Mota-Filipe, H.; Thiemermann, C.

In: Kidney International, Vol. 62, No. 4, 2002, p. 1249-1263.

Research output: Contribution to journalArticle

Chatterjee, PK, Zacharowski, K, Cuzzocrea, S, Brown, PAJ, Stewart, KN, Mota-Filipe, H & Thiemermann, C 2002, 'Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury', Kidney International, vol. 62, no. 4, pp. 1249-1263. https://doi.org/10.1111/j.1523-1755.2002.kid580.x
Chatterjee PK, Zacharowski K, Cuzzocrea S, Brown PAJ, Stewart KN, Mota-Filipe H et al. Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury. Kidney International. 2002;62(4):1249-1263. https://doi.org/10.1111/j.1523-1755.2002.kid580.x
Chatterjee, P. K. ; Zacharowski, K. ; Cuzzocrea, S. ; Brown, Paul Anthony James ; Stewart, Keith Nicol ; Mota-Filipe, H. ; Thiemermann, C. / Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury. In: Kidney International. 2002 ; Vol. 62, No. 4. pp. 1249-1263.
@article{d940529efaa742c39bfb5cff1bc36d7b,
title = "Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury",
abstract = "Background. The aim of this study was to investigate whether in vivo administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus , protects the kidney against the renal dysfunction and injury caused by ischemia/reperfusion (I/R).Methods. Male Wistar rats were administered LTA from S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were measured for the assessment of renal function, tubular and reperfusion-injury. Renal sections were used for histological grading of renal injury and for immunohistochemical localization of P-selectin, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Nitric oxide (NO) production was determined by measurement of plasma nitrite/nitrate levels.Results. LTA pretreatment significantly reduced renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as well as histological evidence of renal injury. LTA also reduced the expression of P-selectin and kidney MPO activity associated with renal I/R. MDA levels were significantly reduced by LTA pretreatment suggesting a reduction in the lipid peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment also markedly reduced both the expression of iNOS and the formation of nitrotyrosine associated with renal I/R. Although LTA significantly reduced plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels remained at levels significantly higher than that measured from the plasma obtained from Sham-operated animals.Conclusions. These data suggest, to our knowledge for the first time, that LTA pretreatment for 24 hours significantly reduces renal I/R injury. We propose that the mechanism of the protective effect involves reduction of the production of NO, ROS and peroxynitrite subsequent to reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA pretreatment resulted in a reduction of iNOS expression and NO production, we hypothesize that the remaining significant levels of NO contribute to the beneficial actions provided by LTA.",
keywords = "kidney transplantation, reperfusion-injury, Gram positive bacteria, lipopolysaccharide, P-selectin, inducible nitric oxide synthase, nitric oxide, peroxynitrite, NITRIC-OXIDE SYNTHASE, ISCHEMIA-REPERFUSION INJURY, MONOPHOSPHORYL LIPID-A, CELL-ADHESION-MOLECULES, SMOOTH-MUSCLE CELLS, RAT-KIDNEY, PEROXYNITRITE FORMATION, MYOCARDIAL-ISCHEMIA, EPITHELIAL-CELLS, IN-VIVO",
author = "Chatterjee, {P. K.} and K. Zacharowski and S. Cuzzocrea and Brown, {Paul Anthony James} and Stewart, {Keith Nicol} and H. Mota-Filipe and C. Thiemermann",
year = "2002",
doi = "10.1111/j.1523-1755.2002.kid580.x",
language = "English",
volume = "62",
pages = "1249--1263",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Lipoteichoic acid from Staphlococcus aureus reduces renal ischemia /reperfusion injury

AU - Chatterjee, P. K.

AU - Zacharowski, K.

AU - Cuzzocrea, S.

AU - Brown, Paul Anthony James

AU - Stewart, Keith Nicol

AU - Mota-Filipe, H.

AU - Thiemermann, C.

PY - 2002

Y1 - 2002

N2 - Background. The aim of this study was to investigate whether in vivo administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus , protects the kidney against the renal dysfunction and injury caused by ischemia/reperfusion (I/R).Methods. Male Wistar rats were administered LTA from S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were measured for the assessment of renal function, tubular and reperfusion-injury. Renal sections were used for histological grading of renal injury and for immunohistochemical localization of P-selectin, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Nitric oxide (NO) production was determined by measurement of plasma nitrite/nitrate levels.Results. LTA pretreatment significantly reduced renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as well as histological evidence of renal injury. LTA also reduced the expression of P-selectin and kidney MPO activity associated with renal I/R. MDA levels were significantly reduced by LTA pretreatment suggesting a reduction in the lipid peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment also markedly reduced both the expression of iNOS and the formation of nitrotyrosine associated with renal I/R. Although LTA significantly reduced plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels remained at levels significantly higher than that measured from the plasma obtained from Sham-operated animals.Conclusions. These data suggest, to our knowledge for the first time, that LTA pretreatment for 24 hours significantly reduces renal I/R injury. We propose that the mechanism of the protective effect involves reduction of the production of NO, ROS and peroxynitrite subsequent to reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA pretreatment resulted in a reduction of iNOS expression and NO production, we hypothesize that the remaining significant levels of NO contribute to the beneficial actions provided by LTA.

AB - Background. The aim of this study was to investigate whether in vivo administration of a low, sub-lethal dose of lipoteichoic acid (LTA), a bacterial wall-fragment derived from the Gram-positive bacterium Staphylococcus aureus , protects the kidney against the renal dysfunction and injury caused by ischemia/reperfusion (I/R).Methods. Male Wistar rats were administered LTA from S. aureus (1 mg/kg, IP). After 24 hours, rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion (6 h). Serum and urinary markers were measured for the assessment of renal function, tubular and reperfusion-injury. Renal sections were used for histological grading of renal injury and for immunohistochemical localization of P-selectin, inducible nitric oxide synthase (iNOS) and nitrotyrosine (indicative of peroxynitrite formation). Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Nitric oxide (NO) production was determined by measurement of plasma nitrite/nitrate levels.Results. LTA pretreatment significantly reduced renal dysfunction, tubular and reperfusion-injury caused by I/R of the kidney as well as histological evidence of renal injury. LTA also reduced the expression of P-selectin and kidney MPO activity associated with renal I/R. MDA levels were significantly reduced by LTA pretreatment suggesting a reduction in the lipid peroxidation and formation of reactive oxygen species (ROS). LTA pretreatment also markedly reduced both the expression of iNOS and the formation of nitrotyrosine associated with renal I/R. Although LTA significantly reduced plasma nitrite/nitrate levels associated with I/R, nitrite/nitrate levels remained at levels significantly higher than that measured from the plasma obtained from Sham-operated animals.Conclusions. These data suggest, to our knowledge for the first time, that LTA pretreatment for 24 hours significantly reduces renal I/R injury. We propose that the mechanism of the protective effect involves reduction of the production of NO, ROS and peroxynitrite subsequent to reduced P-selectin and iNOS expression and PMN recruitment. However, although LTA pretreatment resulted in a reduction of iNOS expression and NO production, we hypothesize that the remaining significant levels of NO contribute to the beneficial actions provided by LTA.

KW - kidney transplantation

KW - reperfusion-injury

KW - Gram positive bacteria

KW - lipopolysaccharide

KW - P-selectin

KW - inducible nitric oxide synthase

KW - nitric oxide

KW - peroxynitrite

KW - NITRIC-OXIDE SYNTHASE

KW - ISCHEMIA-REPERFUSION INJURY

KW - MONOPHOSPHORYL LIPID-A

KW - CELL-ADHESION-MOLECULES

KW - SMOOTH-MUSCLE CELLS

KW - RAT-KIDNEY

KW - PEROXYNITRITE FORMATION

KW - MYOCARDIAL-ISCHEMIA

KW - EPITHELIAL-CELLS

KW - IN-VIVO

U2 - 10.1111/j.1523-1755.2002.kid580.x

DO - 10.1111/j.1523-1755.2002.kid580.x

M3 - Article

VL - 62

SP - 1249

EP - 1263

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -