Glomerular deposition of alpha 2-macroglobulin in glomerular diseases

BACKGROUND: alpha 2-macroglobulin (alpha 2M) 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 2M in glomerular disease has not been extensively studied. The amount, frequency and local distribution of alpha 2M in diseased glomeruli are similarly undetermined. METHODS: Two hundred and fifty renal biopsy cases with glomerular disease were collected. The glomerular deposition of alpha 2M was surveyed with immunofluorescence-microscopy and intraglomerular localization of alpha 2M was assessed by immunoelectron-microscopy. To clarify the relationship between circulatory concentration and local deposition of alpha 2M, serum samples were collected at time of biopsy and alpha 2M was determined using radial immunodiffusion assay. RESULTS: The amount and frequency of local deposition of alpha 2M 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 2M concentration but also exhibited higher frequency of glomerular deposition of alpha 2M (25.9 and 30% respectively). The local deposition of alpha 2M revealed by optical and electron-microscopy may not be directly related to the high serum level of alpha 2M. The deposited alpha 2M 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 2M in glomerular disease. The relatively selective deposition of alpha 2M in some glomerular diseases strongly indicates that alpha 2M may play an active role in the modulation of local inflammatory reaction and tissue repair in these glomerular diseases.