Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Background. Anaphylatoxin C5a mediates inflammatory responses through inter action with a specific C5a receptor (C5aR). the expression of which is thou ght to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recent ly been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined. Methods. Immunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with vari ous renal diseases, including 4 with minimal change nephrotic syndrome (MCN S), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy. 5 with non-Ig A mesGN, and 5 with lupus nephritis). Normal portions of surgically resecte d kidney served as the control. Results. In normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epi thelial cells, and vascular endothelial and smooth muscle cells. In MCNS, t he distribution of C5aR protein and mRNA was similar to that in normal kidn eys. In MN and mesGN. C5aR protein and mRNA were detected in mesangial cell s, glomerular epithelial and endothelial cells, Bowman's capsule cells. tub ular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positi vely with the degree of mesangial hypercellularity and mesangial matrix exp ansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and intersti tial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine. Conclusions. Our results indicate that renal cells produce C5aR and that ac tivation of C5a/C5aR pathway on renal cells may be involved in tissue injur y in mesGN.