Cyclosporin A reduces expression of adhesion molecules in the kidney of rats with chronic serum sickness.
Treatment with cyclosporin A (CsA) improves proteinuria and reduces renal cellular infiltration in chronic serum sickness (CSS). We examined if these effects were associated with a reduced renal expression of CD54 and its ligands, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and MHC class II molecules. We studied two groups of rats in which CSS was induced by daily injections of ovalbumin (OVA): a group treated with CsA (OVA.CsA group, n = 11) and a group that received no treatment (OVA.CSS group, n = 11). An additional group of five rats (control group) received only phosphate buffer. Immunostaining techniques were used to follow CSS and to study the expression of CD54, CD18, CD11b/c, IFN-gamma, TNF-alpha and MHC class molecules. Proteinuria (mg/24 h) was reduced from 248.2 +/- 73.1 (OVA.CCS group) to 14.5 +/- 13.1 with CsA treatment (P < 0.0001). The renal expression of CD54 and its ligands (CD18 and CD11b/c) was reduced by 50% to 75%. Correspondingly, there was a 60% to 85% reduction in the number of infiltrating leucocytes. The number of cells expressing TNF-alpha, IFN-gamma and MHC II molecules was also reduced. CsA reduces expression of CD54 and its ligands. This effect is associated with a reduction of cellular infiltration, IFN-gamma, TNF-alpha-producing cells and with MHC II expression in the kidney. These findings suggest that expression of adhesion molecules plays a critical role in CSS and underline the importance of cellular immunity in this experimental model.
Department of Immunobiology, Instituto de Investigaciones Biomédicas, Fundacite-Zulia, Centro de Cirugía Experimental, Universidad del Zulia and Servicio de Nefrología, Hospital Universitario, Maracaibo, Venezuela.
J
J
Rincón
G
G
Parra
Y
Y
Quiroz
L
L
Benatuil
B
B
Rodríguez-Iturbe
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D006649:Histocompatibility Antigens / Q000096:biosynthesis / Q000235:genetics; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000209:etiology; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D009393:Nephritis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012713:Serum Sickness / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015815:Cell Adhesion Molecules; D006649:Histocompatibility Antigens; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C038353:histocompatibility antigens RT, rat; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016572:Cyclosporine; D010047:Ovalbumin; D003404:Creatinine