title: Macromolecular properties that promote mesangial binding and mesangiopathic nephritis.
abstract: The hydrodynamic size, electrostatic charge, and specificity are established determinants of the site of glomerular localization of macromolecules. Larger macromolecules or aggregates and anionic charge are associated with mesangial deposits, despite the fact that the mesangial matrix bears a negative charge similar to that of the capillary wall. Antigens such as Sendai virus, a model infectious pathogen, gliadin, a model dietary/environmental agent and fibronectin, a model endogenous macromolecule, bind to mesangial cells in vitro on the basis of cell surface glycoconjugates. Nonantibody immunoglobulin A, which does not bind to cells directly, binds to these elements via different carbohydrate specificities (simple sugar inhibition). Such binding promotes or augments macromolecular deposition in the mesangium. More significantly, mesangial deposits per se are not pathogenic, because normal renal function can be observed with florid deposits. Pathogenic deposits must have properties that alter mesangial cell metabolism or interaction with the matrix. Although complement activation is well recognized, complement-independent mechanisms related to cell surface modulation are being recognized. In vitro, antigen/immunoglobulin A aggregates alter mesangial cell eicosanoid synthesis. In vivo, large-lattice cross-linking by particulate antigen promotes hematuria. We conclude that the binding of macromolecules to cells and the cross-linking of cell surface molecules cause alterations in the mesangial cells and therefore in glomerular function. The mesangial cell, rather than a passive respondent, is an active participant in the genesis of glomerulonephritis.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH 44106.
authors.forename: S N
authors.initials: SN
authors.lastname: Emancipator
authors.forename: C S
authors.initials: CS
authors.lastname: Rao
authors.forename: A
authors.initials: A
authors.lastname: Amore
authors.forename: R
authors.initials: R
authors.lastname: Coppo
authors.forename: J G
authors.initials: JG
authors.lastname: Nedrud
mesh_terms: D000818:Animals; D001665:Binding Sites; D005920:Glomerular Mesangium / Q000378:metabolism*; D005921:Glomerulonephritis / Q000209:etiology* / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000209:etiology; D006801:Humans; D037102:Lectins / Q000378:metabolism; D046911:Macromolecular Substances
chemical_list: D037102:Lectins; D046911:Macromolecular Substances