Membrane Attack Complex and Membrane Cofactor Protein Are Related to Tubulointerstitial Inflammation in Various Human Glomerulopathies

Abstract

Immunohistochemical analysis of the membrane attack complex (MAC) and the membrane cofactor protein (MCP) was performed on the tubuli and cortical vessels of 46 kidney biopsies with various types of human glomerulopathies. Irrespective of the type of glomerulopathy, significant correlations between tubular MAC and interstitial lymphomonocyte infiltration (p < 0.001) and interstitial volume (p < 0.02) were found. Tubular MCP was significantly overexpressed at the site of MAC deposition (p < 0.002). There was no correlation between the vascular MAC and MCP and tubulointerstitial lesions. Since tubular MAC is deposited in inflamed areas of tubulointerstitium, we propose that MAC might contribute to the development of tubulointerstitial inflammatory processes in human glomerulopathies. MCP as a regulatory factor in the tubulointerstitium might abrogate further tissue damage and cell-stimulatory effects of the MAC.

Urine Levels of CD46 (Membrane Cofactor Protein) Are Increased in Patients with Glomerular Diseases

“…In fact, membrane MCP in the kidney is also up-regulated in some disease states such as IgA nephropathy (28). Another report (29) has suggested that tubular MCP is overexpressed at the deposition site of the membrane attack complex. The levels of sMCP were increased in patients with malignancy (19) and autoimmune diseases such as systemic lupus erythematosus (30).…”

C3a Mediates Epithelial-to-Mesenchymal Transition in Proteinuric Nephropathy

“…15 There is a spatial association between complement deposition and tissue injury in the kidneys of patients with proteinuric nephropathies. 16 In experimental proteinuria, genetic deficiency, [17][18][19] or depletion or inhibition 20,21 of complement reduces the level of tubulointerstitial injury and preserves renal function. 22 These data support a role for both C5b-9 19 and the anaphylotoxin C5a.…”

Complement C5 Mediates Experimental Tubulointerstitial Fibrosis

“…For example, elevated urinary C5b-9 concentrations are found in proteinuric patients (2), urinary C5b-9 was shown to reflect disease activity in an experimental model of membranous glomerulonephritis better then proteinuria (3), C5b-9 depletion in experimental nephropathy reduces proteinuria (4), and C5b-9 is formed at sites of tubulointerstitial injury (5,6).…”