title: Effect of anti-ICAM-1 antibodies on macromolecular leakage and leukocyte activation: a study of hindlimb allografts in the rat.
abstract: We investigated the ability of anti-ICAM-1 monoclonal antibodies to reduce endothelial cell damage by assessing microvascular permeability and microcirculatory function during the acute phase of allograft rejection. The composite rat hindlimb-cremaster muscle transplantation model was employed in three experimental groups of 18 animals each. Isograft control transplantations were performed between genetically identical Lewis (LEW, RT11) rats. Allograft transplantations were performed across a major histocompatibility barrier between Lewis-Brown-Norway (LBN, RT-11+n), and Lewis (LEW, RT11) rats. In addition, a third group of animals receiving allografts was treated with 1 mg/kg/day of anti-ICAM-1 monoclonal antibody. After 24 hours, 72 hours, and 7 days, we measured microvascular permeability, leukocyte activation, functional capillary perfusion, red blood cell velocity, vessel diameters, and endothelial edema index in six animals per each follow-up period. Endothelial cell damage was assessed by measuring graft permeability to fluorescein isothiocyanate-labeled albumin (0.2 ml/100 g body weight) with computer-aided image analysis. Mean microvascular permeability was lower in the treated allograft group than in untreated controls at all follow-up times (p<0.001). In addition, anti-ICAM-1 treatment significantly reduced the activation of sticking leukocytes at 24 and 72 hours (p<0.001) and the activation of transmigrating leukocytes at 72 hours and 7 days (p<0.05). The allografts presented a characteristic microcirculatory pattern of acute rejection as early as 24 hours after transplantation. The dysfunction of the endothelial cell barrier at all time points was indicated by significant increases in the degree of allograft macromolecular permeability and in the number of activated sticking and transmigrating leukocytes. Treatment with anti-ICAM-1 antibodies significantly reduced the surge of leukocytes in the allograft transplants and protected the endothelial barrier from the acute effects of transplantation trauma.
authors.affiliation: Department of Orthopedics and Traumatology at Ankara Hospital, Cleveland, Ohio, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gudemez
authors.forename: M
authors.initials: M
authors.lastname: Turegun
authors.forename: K
authors.initials: K
authors.lastname: Carnevale
authors.forename: J
authors.initials: J
authors.lastname: Zins
authors.forename: M
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000502:physiology; D006084:Graft Rejection / Q000473:pathology*; D006614:Hindlimb; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000637:transplantation; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013524:Surgical Flaps / Q000098:blood supply*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1