Glomerular cells do not express the C5a receptor in human glomerulonephritis.

Letters Glomerular cells do not express the C5a receptor in human glomerulonephritis Sir, Complement is a major mediator of glomerular inflammation in several form of glomerulonephritis such as lupus nephritis, membranous nephritis, anti-GBM nephritis, or IgA nephro-pathy. Activation of the terminal pathway leads to cleavage of C5 and release of the potent anaphylatoxin C5a. C5a and its catabolite C5a(desArg) mediate their potent pro-inflammatory effects through binding to the C5a receptor CD88. The G-protein-coupled receptor is expressed mainly by cells of myeloid origin such as macrophages and neutro-phils. CD88 expression has also been reported in lung, liver, and brain tissue [1]. A recent report describes expression of CD88 on cultured human mesangial cells. Stimulation of the receptor caused mildly enhanced proliferation and synthesis of MCP-1 and platelet-derived growth factor (PDGF) [2]. The C5a receptor has also been described on proximal tubular cells and macrophages in normal renal tissue [3]. These reports prompted us to investigate CD88 expression in human renal diseases, mainly glomerulonephritis. Thirty-one consecutive renal biopsies and one normal control tissue from a kidney removed for renal-cell carcinoma were investigated. The diagnostic groups are shown in Table 1. Of the four patients with rapidly progressive glomerulonephritis (RPGN), two had anti-GBM nephritis, one an antineutro-philic cytoplasmic antibody (ANCA)-associated nephritis, and one suffered from Henoch–Schö nlein purpura. The biopsies were investigated using the direct immunofluores-cence method. Five-micrometre-thick acetone-fixed cryostat section were incubated with two well-characterized mono-clonal anti-CD88 antibodies P12/11 (2 mg/ml) and D12/1 (4 mg/ml) for 30 min [3]. In addition, a mouse monoclonal (a) (b) anti-leukocyte common antigen–antibody was used to stain Fig. 1. (a) Expression of CD88 on proximal tubular epithelial cells all leukocytes. After washing in phosphate-buffered saline a in a case of membranous nephropathy (×200). (b) Staining of fluorescein isothiocyanate (FITC)-conjugated polyclonal intraglomerular leukocytes in a case of Goodpasture's syndrome (×400). rabbit-anti-mouse immunoglobulin antibody was applied. In normal renal tissue we found CD88 on proximal tubular epithelial cells with some predominance on the basolateral were CD88 positive. No staining of intrinsic glomerular cells membrane (Figure 1a). In addition a few interstitial cells was observed in normal renal tissue or in all cases of glomerulonephritis or interstitial nephritis. Tubular staining was unaltered in most biopsies and reduced only in areas of Table 1. CD88 expression of leukocytes per glomerular cross-section severe tubular damage. The only cells in the glomeruli expressing CD88 were infiltrating leukocytes (Figure 1b). Diagnosis (n=number of …