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- Title
Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia.
- Authors
De Greef, Kathleen E.; Ysebaert, Dirk K.; Dauwe, Simonne; Persy, Veerle; Vercauteren, Sven R.; Mey, Denise; De Broe, Marc E.
- Abstract
Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia. Background. Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both B7-1 and B7-2 costimulatory molecules, protects the kidney during acute ischemia/reperfusion injury. This study investigated whether and how B7-1 and/or B7-2 proteins are involved in renal ischemia/reperfusion injury (IRI). Methods. Uninephrectomized rats were submitted to warm renal ischemia (30 min) and received control monoclonal antibody (mAb; 17E3), anti-B7-1 (3H5), anti-B7-2 (24F), a combination of anti-B7-1/B7-2, or CTLA-4 Ig. Renal function, morphology, and the kinetics of inflammatory cells were studied for a ten-day period. Binding sites of the injected antibodies were detected by secondary staining with anti-mouse Ab. Results. Compared with controls, acute renal failure (ARF) in the anti-B7-1 group was attenuated both functionally and morphologically. Anti-B7-1/B7-2 and CTLA-4 Ig also were protective in IRI. ARF was not altered by anti-B7-2 treatment. Two hours after reperfusion, B7-1 was expressed along the endothelial cells of the ascending vasa recta. Expression of B7-1 increased over time during the first 24 hours and decreased thereafter. Two hours after reperfusion, adherence/accumulation of T cells and monocytes/macrophages was found in the vasa recta of the ischemic kidney. Anti-B7-1–treated animals had fewer T cells and monocytes/macrophages in the vasa recta compared with controls. Leukocyte accumulation in these vessels after anti-B7-2 treatment was not different from IRI controls. Conclusion. These observations strongly support the key role of the B7-1 protein in the protection of renal IRI through inhibition of T cell and monocyte adherence at the level of the ascending vasa recta.
- Subjects
REPERFUSION injury; KIDNEY diseases; PROTEINS; T cells
- Publication
Kidney International, 2001, Vol 60, Issue 4, p1415
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2001.0600041415.x