Cell Biology – Immunology – Pathology
Kidney International (2005) 67, 103–110; doi:10.1111/j.1523-1755.2005.00060.x
Natural history of renal scarring in susceptible mIL-8Rh-/- mice
MAJLIS SVENSSON, HEIKKI IRJALA, PER ALM, BO HOLMQVIST, ANN-CHARLOTTE LUNDSTEDT and CATHARINA SVANBORG
Institute of Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, University of Lund, Lund, Sweden; Department of Otorhinolaryngology, Head and Neck Surgery, University of Turku, Turku, Finland; and Jubileumsinstitutionen, Department of Pathology, University of Lund, Lund, Sweden
Correspondence: Catharina Svanborg, Institute of Laboratory Medicine, Department of Microbiology, Immunology and Glycobiology, Sölvegatan 23, S-22362 Lund, Sweden. E-mail:catharina.svanborg@mig.lu.se
Received 12 May 2004; Revised 24 June 2004; Accepted 9 July 2004.
Abstract
Natural history of renal scarring in susceptible mIL-8Rh-/- mice.
Background
Urinary tract infections (UTIs) cause end-stage renal disease (ESRD) but the molecular mechanisms have remained unclear. Recently, the interleukin (IL)-8 receptor was shown to control disease susceptibility in mice and low IL-8 receptor expression was observed in pyelonephritis-prone patients.
Methods
Intravesical Escherichia coli infection was established in mIL-8Rh-/- or Balb/c control mice. Survival, bacterial persistence, and histology were used as measurements of disease severity.
Results
Within 2 days, 19/30 mIL-8Rh-/- mice developed lethal infection with bacteremia. Surviving mice remained infected and developed progressive renal damage with pathologic neutrophil accumulation and abscess formation first under the pelvic epithelium and then throughout the tissue. Recruited immune effector cells were unable to remove the dying neutrophils and frustrated macrophages formed foam cell aggregates. As a result, there was successive destruction of the mucosal barrier, medulla and cortex and necrosis of the renal papilla. The mIL-8Rh+/+ mice all survived and infection was cleared within a few days without symptoms or tissue pathology.
Conclusion
mIL-8Rh-/- mice develop acute bacteremic pyelonephritis and renal scarring due to a dysfunctional neutrophil response. The tissue damage resembles human disease, and these mice offer a model system to study the molecular mechanisms of renal scarring.
Keywords:
UTI, acute pyelonephritis, renal scarring, host susceptibility, IL-8 receptor deficiency
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