Glomerular deposition of alpha(2)-macroglobulin in glomerular diseases

Background. alpha(2)-macroglobulin (alpha(2)M) is a glycoprotein involved in delivery of growth factors, regulation of matrix degrading enzymes and modulation of fibrinolysis factors, all of which are considered as important pathogenic mechanisms of glomerular injury. However, the role of alpha(2)M in glomerular disease has not been extensively studied. The amount, frequency and local distribution of alpha(2)M in diseased glomeruli are similarly undetermined. Methods. Two hundred and fifty renal biopsy cases with glomerular disease were collected. The glomerular deposition of alpha(2)M was surveyed with immunofluorescence-microscopy and intraglomerular localization of alpha(2)M was assessed by immunoelectron-microscopy. To clarify the relationship between circulatory concentration and local deposition of alpha(2)M, serum samples were collected at time of biopsy and alpha(2)M was determined using radial immunodiffusion assay. Results. The amount and frequency of local deposition of alpha(2)M in glomeruli varied from disease to disease, and the average positive rate was approximately 20%. Patients with minimal-change nephrotic syndrome and IgM nephropathy not only had the highest mean serum alpha(2)M concentration but also exhibited higher frequency of glomerular deposition of alpha(2)M (25.9 and 30% respectively). The local deposition of alpha(2)M revealed by optical and electron-microscopy may not be directly related to the high serum level of alpha(2)M. The deposited alpha(2)M was observed to associate with electron-dense deposits, mesangial matrix and mesangial cells. Conclusions. To our knowledge, this is the first report that reveals the ultrastructural distribution of alpha(2)M in glomerular disease. The relatively selective deposition of alpha(2)M in some glomerular diseases strongly indicates that alpha(2)M may play an active role in the modulation of local inflammatroy reaction and tissue repair in these glomerular diseases.