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.


CONCLUSIONS
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.
De Greef
K E
KE
Department of Experimental Surgery, University of Antwerp, Antwerp, Belgium.
Ysebaert
D K
DK
Dauwe
S
S
Persy
V
V
Vercauteren
S R
SR
Mey
D
D
De Broe
M E
ME
D000069594:Abatacept; D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000494:pharmacology; D001160:Arterioles; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D002448:Cell Adhesion / Q000187:drug effects; D005434:Flow Cytometry; D018796:Immunoconjugates; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000502:physiology*; D009336:Necrosis; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497966:Cd86 protein, rat; C556707:Ctla4 protein, mouse; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept