title: Administration of IgG Fc fragments prevents glomerular injury in experimental immune complex nephritis.
abstract: Most human nephritis is due to glomerular deposition and/or formation of immune complexes (IC). In cultured mesangial cells, Fc receptor stimulation induces proliferation, matrix synthesis, and release of several mediators implicated in the initiation and progression of glomerular injury. Since Ig Fc fragments in vitro modified these phenomena, we studied the effects of systemic administration of IgG Fc fragments on the evolution of experimental IC nephritis. Fc fragment injection (1 mg/day i.p.) to rats with ongoing nephritis (proteinuria 20-50 mg/24 h vs 9 +/- 0.2 mg/24 h in controls) markedly ameliorates proteinuria, renal function, and morphological renal lesions. This was accompanied by a reduction in the renal synthesis of chemokines (monocyte chemoattractant protein-1, IFN-inducible protein-10, and cytokine-induced neutrophil chemoattractant-1), matrix proteins, and growth factors (platelet-derived growth factor, and TGF-beta), and in the activity of transcription factors. The treatment did not affect the glomerular deposition of IgG IC and complement C1q. In contrast, a decrease in the renal expression and production of C3 was observed without changes in serum complement levels. In vitro, very low complement consumption and no C3b covalent interaction were observed with Fc fragments, confirming that they did not modify systemic complement activity. These results indicate that the administration of Fc fragments prevents the development of glomerular damage in an aggressive model of proliferative glomerulonephritis through mechanisms involving a reduced local generation of complement, chemokines and growth factors. Modulation of IC-mesangial cell interaction by Fc fragment administration could represent a new approach to the treatment of severe immune nephritis.
authors.affiliation: Renal Research Laboratory, Department of Immunology, Fundación Jiménez Díaz, Autonoma University, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Guerrero
authors.forename: N
authors.initials: N
authors.lastname: Duque
authors.forename: M T
authors.initials: MT
authors.lastname: Casado
authors.forename: C
authors.initials: C
authors.lastname: Pastor
authors.forename: J
authors.initials: J
authors.lastname: Blanco
authors.forename: F
authors.initials: F
authors.lastname: Mampaso
authors.forename: F
authors.initials: F
authors.lastname: Vivanco
authors.forename: J
authors.initials: J
authors.lastname: Egido
mesh_terms: D000818:Animals; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007105:Immune Complex Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007684:Kidney Tubules / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity / Q000276:immunology; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018925:Chemokines; D003176:Complement C3; D016326:Extracellular Matrix Proteins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014157:Transcription Factors; D016212:Transforming Growth Factor beta