RGD Reference Report - Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion. - Rat Genome Database

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Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion.

Authors: Cugini, D  Azzollini, N  Gagliardini, E  Cassis, P  Bertini, R  Colotta, F  Noris, M  Remuzzi, G  Benigni, A 
Citation: Cugini D, etal., Kidney Int. 2005 May;67(5):1753-61.
RGD ID: 7257683
Pubmed: PMID:15840022   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1523-1755.2005.00272.x   (Journal Full-text)

BACKGROUND: Ischemia/reperfusion (I/R) injury after organ transplantation is a major cause of delayed graft function. Following I/R, locally produced CXC chemokines attract and activate granulocytes, which in turn promote graft damage. METHODS: We examined the involvement of granulocyte recruitment via the CXCR2 pathway in a rat model of 4 hours cold ischemia followed by kidney transplantation. Serum creatinine and intragraft granulocyte infiltration were monitored in the early phase posttransplant. A CXCR2 inhibitor, repertaxin, was given to recipients before transplantation (at -24 hours or -8 hours or -2 hours), immediately before reperfusion and 2 hours later. RESULTS: An increase of granulocyte chemoattractant CINC-1/interleukin-8 (IL-8) mRNA expression after I/R both in syngeneic and allogeneic transplantation was associated with a marked infiltration of granulocytes in renal tissue. In syngeneic transplantation, Lewis rats given 15 mg/kg repertaxin 24 hours before surgery had granulocyte graft infiltration and serum creatinine levels significantly reduced in respect to vehicle-treated animals. Intermediate effects were observed with 5 mg/kg, whereas the dose of 30 mg/kg had toxic effects. We found that reducing the pretreatment time to 8 hours before surgery was still effective. Prevention of granulocyte infiltration and serum creatinine increase was also obtained in allogeneic transplantation, when Brown Norway recipients of Lewis kidneys were given 15 mg/kg repertaxin starting 8 hours before surgery. CONCLUSION: Repertaxin treatment of the recipient animal was effective in preventing granulocyte infiltration and renal function impairment both in syngeneic and in allogeneic settings. The possibility to modulate I/R injury in this rat model opens new perspectives for preventing posttransplant delayed graft function in humans.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Transplant Rejection  ISOCxcr2 (Rattus norvegicus)7257683; 7257683 RGD 
Transplant Rejection  IMP 7257683 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Mus musculus)
Cxcr2  (C-X-C motif chemokine receptor 2)

Genes (Homo sapiens)
CXCR2  (C-X-C motif chemokine receptor 2)


Additional Information