DISTRIBUTION OF EXTRACELLULAR-MATRIX RECEPTORS IN VARIOUS FORMS OF GLOMERULONEPHRITIS

Integrins are heterodimeric transmembrane receptor glycoproteins consi sting of alpha and beta subunits that mediate adhesion and interaction s between cells and extracellular matrix. Such interactions may be per turbed in various pathologic states, resulting in the altered phenotyp ic expressions of the integrins in affected tissues. To ascertain the alterations in integrins in various renal diseases, their distribution was investigated in different forms of glomerulonephritis by indirect immunofluorescence and immunoelectron microscopy using specific antib odies directed against beta(1) integrins and integrin alpha(v) beta(3) (vitronectin receptor). In addition, the distribution of certain extr acellular matrix components (ie, fibronectin, vitronectin, and type IV collagen) was examined. Integrin beta(1) and alpha(v) beta(3) were hi ghly expressed in proliferating mesangial cells in immunoglobulin A ne phropathy, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. Their putative ligands (ie, fibronecti n, vitronectin, and type IV collagen) also were increased in the expan ded mesangial regions. In immunoglobulin A nephropathy, integrin beta( 1) and alpha(v) beta 3 were seen by immunoelectron microscopy to be lo calized to the mesangial cell membranes in close proximity to the immu ne complex deposits; however, fibronectin and vitronectin immunoreacti vities were observed in the mesangial immune complex deposits. Similar ly, vitronectin also was detected in the immune complex deposits of ot her forms of proliferative nephritis, ie, membranoproliferative glomer ulonephritis type I and diffuse proliferative lupus nephritis. In diff use proliferative lupus nephritis, the cellular crescents displayed im munoreactivity toward integrin alpha(v) beta(3) and vitronectin. In no nimmune complex glomerular disease associated with nephrotic syndrome (ie, minimal change nephrotic syndrome), integrin alpha(3) beta(1) whi ch normally has a linear capillary distribution, was decreased. In imm une complex nephritis associated with nephrotic syndrome (ie, membrano us nephropathy), integrin alpha(3) beta(1) immunoreactivity was focall y disrupted and capillary loops displayed a discontinuous linear distr ibution. Finally, in membranous nephropathy, immunoreactivity toward v itronectin was accentuated in immune complex deposits. The differentia l altered distributions of the integrins and of their ligands may be r eflective of mesangial cell proliferative activity in certain forms of glomerulonephritis, while in other forms of glomerular diseases, the decreased immunoreactivity of integrin alpha(3) beta(1) may be related to the glomerular capillary wall alterations associated with proteinu ric states. (C) 1995 by the National Kidney Foundation, Inc.