Protective role of selectin ligand inhibition in a large animal model of kidney ischemia-reperfusion injury

Autor: Séverine Deretz, Gérard Mauco, Jean-Pierre Richer, Hamid Rabb, T. Hauet, Frédéric Favreau, Christophe Jayle, Carole Doucet, S. Milinkevitch
Přispěvatelé: ProdInra, Migration, Génétique Expérimentale en Productions Animales (GEPA), Institut National de la Recherche Agronomique (INRA)
Rok vydání: 2006
Předmět:
Nephrology
Male
Pathology
Swine
[SDV]Life Sciences [q-bio]
T-Lymphocytes
030232 urology & nephrology
urologic and male genital diseases
Kidney
Ligands
0302 clinical medicine
Fibrosis
PIGS
ComputingMilieux_MISCELLANEOUS
0303 health sciences
Molecular Structure
Immunohistochemistry
3. Good health
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Mannosides
Reperfusion Injury
Selectin
medicine.medical_specialty
T lymphocytes
ISCHEMIE-REPERFUSION
Protective Agents
03 medical and health sciences
Internal medicine
medicine
Animals
cardiovascular diseases
renal ischemia
selectin
030304 developmental biology
Renal ischemia
TRANSPLANTATION
urogenital system
business.industry
Biphenyl Compounds
medicine.disease
Disease Models
Animal
Endocrinology
Tubulointerstitial fibrosis
Selectins
Nephritis
Interstitial
business
Reperfusion injury
Mannose
ISCHEMY-REPERFUSION
Kidney disease
Zdroj: Kidney International
Kidney International, Nature Publishing Group, 2006, 69, pp.1749-1755
ISSN: 0085-2538
1523-1755
Popis: Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuates IRI, cellular inflammation, and long-term effects on renal interstitial fibrosis. We used a porcine model of kidney IRI and used Texas Biotechnology Corporation (TBC)-1269, a selectin ligand inhibitor. Renal function, tissue inflammation, and tubulointerstitial fibrosis development were evaluated up to 16 weeks. Both warm and cold ischemia models were studied for relevance to native and transplant kidney injury. Pigs treated with TBC-1269 during 45 min of warm ischemia (WI) showed significantly increased glomerular filtration rate compared to control animals. In pigs with severe IRI (WI for 60 min), TBC-1269 treatment during IRI significantly increased renal recovery. Cellular inflammation was strongly reduced, particularly influx of CD4 cells. Quantitative measurement of fibrosis by picrosirius red staining showed strong reduction in TBC-1269-treated groups. TBC-1269 also reduced cold IRI, inflammation, and fibrosis in kidneys preserved for 24 h at 4 degrees C and autotransplanted. The selectin ligand inhibitor TBC-1269 provides a novel and effective approach to attenuate IRI in both warm and cold ischemia in large mammals, in both short and long terms. Selectin ligand inhibition is an attractive strategy for evaluation in human kidney IRI.
Databáze: OpenAIRE
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