In vivo effects of monoclonal antibodies against rat beta(2) integrins on kidney ischemia-reperfusion injury.
BACKGROUND
Ischemia-reperfusion (IR) involves adhesion of leukocytes to the activated endothelium, leading to tissue damage. CD11/CD18 beta(2) integrins interact with their ligands on endothelial cells and may therefore represent a therapeutic target for the prevention of IR. We investigated the effects of three monoclonal antibodies (mAbs) that recognize epitopes of heavy or light chain of the beta(2) integrins on IR in kidneys.


METHODS
Uninephrectomized Fischer rats were subjected to 45 or 60 min of renal ischemia, treated with intravenously anti-beta(2) integrin monoclonal antibodies (anti-CD11a, anti-CD11b, and anti-CD18) 5 min prior to reperfusion, and compared to a nontreated group. Serum creatinine, blood urea nitrogen (BUN), and kidney histopathological damages were assessed at 1, 2, and 7 days after ischemia.


RESULTS
After 45 and 60 min of ischemia, serum creatinine and BUN were significantly higher in the control than in animals treated with anti-CD11a and anti-CD18 at 24 and 48 h. Administration of anti-CD11b had a beneficial effect on renal function after 45 min but not after 60 min of ischemia. Histologic and immunostaining studies demonstrated mild tubular necrosis and less leukocyte infiltration in the anti-CD11a- and anti-CD18-treated groups compared to the control group.


CONCLUSIONS
These results indicate that selected antibodies to CD11a/CD18 may decrease kidney IR injury when administered prior to reperfusion.
Tajra
L C
LC
INSERM, Unité 281, Laboratoire de Recherche Chirurgicale, Hôpital Edouard Herriot, Lyon, France.
Martin
X
X
Margonari
J
J
Blanc-Brunat
N
N
Ishibashi
M
M
Vivier
G
G
Panaye
G
G
Steghens
J P
JP
Kawashima
H
H
Miyasaka
M
M
Treille-Ritouet
D
D
Dubernard
J M
JM
Revillard
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology*; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1