title: Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury.
abstract: BACKGROUND
  The role of inflammatory leukocytes in acute renal failure (ARF) remains controversial and appears largely uninvestigated in toxic (in contrast to ischemic) ARF.
  
  
  METHODS
  Female Wistar rats were injected with monoclonal antibodies (mAbs) directed to both the leukocyte function-associated antigen 1 (LFA-1) and the intercellular adhesion molecule 1 (ICAM-1). Doses (6 mg/kg of each mAb) were given 24 hours prior to the induction of acute tubular necrosis (ATN) by mercuric chloride administration (2 mg/kg, subcutaneously, day 0) and subsequently every 48 hours. Control rats similarly received either control antibody (12 mg/kg) or vehicle prior to and following the induction of ATN. Renal function was also measured from male Lewis rats that were similarly treated with anti-adhesion antibodies during exposure to 30 minutes of unilateral renal ischemia.
  
  
  RESULTS
  Injected antibodies were demonstrated on peripheral blood leukocytes (flow cytometrical detection of mouse anti-LFA-1) and on endothelium (immunohistochemical staining of mouse anti-ICAM-1) and were measured in serum (enzyme-linked immunosorbent assay). Macrophages and T cells were prominent in the kidney of control treatment rats after HgCl2 injection, but anti-adhesion treatment clearly had prevented their infiltration. Notwithstanding, renal tubular injury was equally pronounced in all mercuric chloride treatment groups and so was the decline in renal function (serum creatinine, proteinuria). Tubular epithelial cell proliferation seemed slightly less pronounced and delayed in anti-adhesion treated rats. Kidneys from ischemia exposed rats were, however, functionally protected by identical anti-ICAM-1/anti-LFA-1 treatment.
  
  
  CONCLUSIONS
  Prevention of cellular infiltration by mAbs to LFA-1 and ICAM-1 has no effect on renal morphology, function, or regeneration following mercuric chloride-induced ARF in the rat. This result contrasts with the functional protection of the rat kidney to ischemia/reperfusion injury by virtue of an identical antibody treatment protocol. Resolving that controversy should bring better insight in fundamental processes underlying different types of ARF, and will be the subject of further study.
authors.affiliation: Department of Nephrology-Hypertension, University of Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Ghielli
authors.forename: W A
authors.initials: WA
authors.lastname: Verstrepen
authors.forename: K E
authors.initials: KE
authors.lastname: De Greef
authors.forename: M H
authors.initials: MH
authors.lastname: Helbert
authors.forename: D K
authors.initials: DK
authors.lastname: Ysebaert
authors.forename: E J
authors.initials: EJ
authors.lastname: Nouwen
authors.forename: M E
authors.initials: ME
authors.lastname: De Broe
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004202:Disinfectants / Q000633:toxicity*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007684:Kidney Tubules / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D011507:Proteinuria / Q000139:chemically induced / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: D000911:Antibodies, Monoclonal; D004202:Disinfectants; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008627:Mercuric Chloride; D003404:Creatinine