Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury.
BACKGROUND
CD11/CD18 beta(2) integrins are involved in leukocyte adhesion to the activated endothelium, and therefore represent a possible therapeutic target in the prevention of ischaemic acute renal failure (ARF).


METHODS
To assess the effect of an anti-CD11b monoclonal antibody (mAb) in ischaemic ARF, uninephrectomized Fischer rats were subjected to 45 or 60 min of warm renal ischaemia, then received 1 mg of anti-CD11b mAb 5 min before reperfusion.


RESULTS
After 45 min of ischaemia, renal function tests at 24 and 48 h were less altered in mAb-treated than in control rats, but after 60 min of ischaemia the same level of renal insufficiency was observed in the two groups. In parallel, milder tubular necrosis and less leukocyte infiltration were observed in the treated group after 45 min of ischaemia, but no difference was seen after 60 min compared to the control group. The mAb was detected on blood neutrophils up to 48 h after infusion and a marked down-regulation of CD11b expression on neutrophil surfaces was documented by flow cytometry.


CONCLUSIONS
These results indicate that anti-CD11b mAb administered prior to reperfusion decreases moderate ischaemic ARF but fails to prevent renal injury secondary to prolonged ischaemia in this model.
Tajra
L C
LC
INSERM, Unité 281, Laboratoire de Recherche Chirurgicale, Lyon, France.
Martin
X
X
Margonari
J
J
Blanc-Brunat
N
N
Ishibashi
M
M
Vivier
G
G
Steghens
J P
JP
Kawashima
H
H
Miyasaka
M
M
Dubernard
J M
JM
Revillard
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015536:Down-Regulation; D005434:Flow Cytometry; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D012079:Renal Circulation; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen