Age-dependent Role of Microvascular Endothelial and Polymorphonuclear Cells in Lipopolysaccharide-induced Acute Kidney Injury

Francis M. Wulfert, Matijs van Meurs, Neng F. Kurniati, Rianne M. Jongman, Martin C. Houwertjes, Peter Heeringa, Michel M. R. F. Struys, Jan G. Zijlstra*, Grietje Molema

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

Abstract

Background: The incidence of acute kidney injury following severe sepsis is higher in the elderly. We hypothesized that microvascular endothelium is "primed" by aging and that sepsis represents a "second hit," resulting in more severe microvascular complications.

Methods: Three- and 18-months-old mice were intraperitoneally injected with 1,500 EU/g body weight lipopolysaccharide and sacrificed after 8 h. Flow cytometry and myeloperoxidase ELISA determined neutrophils in plasma. Quantitative reverse transcription polymerase chain reaction was used to analyze messenger ribonucleic acid levels of cell adhesion molecules P-selectin and E-selectin, vascular cell adhesion protein-1, intercellular adhesion molecule-1, angiopoietin receptor TIE-2, and angiopoietins Ang1 and Ang2. In kidney tissue we assessed neutrophil influx and E-selectin protein expression. Neutrophils were depleted with the monoclonal antibody NIMP.

Results: At basal conditions, microvascular endothelial cell activation status was similar in both groups, except for a higher Ang-2 expression (P <0.05) in the kidney of aged mice. Lipopolysaccharide-induced increase in neutrophil count was higher in old (3.3-fold change) compared with young mice (2.2-fold change). Messenger ribonucleic acid analysis showed higher upregulation of P- and E-selectin (P = 0.0004, P = 0.0007) after lipopolysaccharide administration in kidneys of elderly mice, which was confirmed at the protein level for E-selectin. Renal neutrophil influx in lipopolysaccharide-treated aged mice was increased (2.5-fold induction in aged and 2.1-fold in young, P <0.0001). Polymorphonuclear cell depletion exaggerated the lipopolysaccharide-induced kidney injury.

Conclusion: Ang-2 is increased in older mice, which might cause priming of the endothelial cells. Endothelium responded by a more extensive increase in expression of P- and E-selectin in older mice and increased polymorphonuclear cell influx.

Original languageEnglish
Pages (from-to)126-136
Number of pages11
JournalAnesthesiology
Volume117
Issue number1
DOIs
Publication statusPublished - Jul-2012
EventAnnual Meeting of American-Society-of-Anesthesiologists (ASA) - , Israel
Duration: 16-Oct-2011 → …

Keywords

  • ACUTE-RENAL-FAILURE
  • TNF-ALPHA
  • SEPSIS
  • MICE
  • NEUTROPHILS
  • INDUCTION
  • ENDOTOXEMIA
  • ACTIVATION
  • MORTALITY
  • SHOCK

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