PMID- 9844130 OWN - NLM STAT- MEDLINE DCOM- 19990211 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 54 IP - 5 DP - 1998 Nov TI - Cultured human glomerular mesangial cells express the C5a receptor. PG - 1542-9 AB - BACKGROUND: While the association of complement activation and glomerulonephritis has been recognized for decades, the pathogenic mechanisms of complement-mediated glomerular damage are incompletely understood. Expression of the C5a receptor in the kidney suggests that C5a could play a direct role in initiating or promoting glomerulonephritis. METHODS: Expression of the C5a receptor by cultured human glomerular mesangial cells (HGMC) was examined by immunofluorescence, by FACS analysis and by reverse transcriptase-polymerase chain reaction (RT-PCR). Potential mitogenic effects were examined by analysis of neutral red dye uptake after treatment with recombinant C5a (rC5a). The production of cytokines [interleukin-1 (IL-1), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1)] and growth factors [transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF-AB)] by mesangial cells stimulated with rC5a was examined by ELISA of cell culture supernatants. RESULTS: Expression of the C5a receptor by the cultured HGMC was demonstrated by both immunofluorescence and FACS. The presence of mRNA encoding the receptor was confirmed by RT-PCR. Treatment of HGMC in vitro with rC5a resulted in mild cellular proliferation. No IL-1 was detected despite stimulation with up to 100 nM rC5a. Concentrations of IL-8 and TGF-beta did not increase beyond basal levels in control samples at any level of stimulation. Mean MCP-1 concentrations and PDGF-AB concentrations increased by 40% and 70% above control values 48 hours post-stimulation (P = 0.01 and P = 0.003, respectively). CONCLUSIONS: These data indicate that the C5a receptor is expressed on HGMC in vitro, and may play a role in mediating glomerular injury by promoting cellular proliferation and the production of cytokines and growth factors. FAU - Braun, M AU - Braun M AD - Division of Nephrology, Children's Hospital Research Foundation, Cincinnati, Ohio, USA. FAU - Davis, A E 3rd AU - Davis AE 3rd LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Antigens, CD) RN - 0 (Chemokine CCL2) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Receptor, Anaphylatoxin C5a) RN - 0 (Receptors, Complement) RN - 80295-54-1 (Complement C5a) SB - IM MH - Antigens, CD/*analysis/genetics/physiology MH - Cell Division MH - Cells, Cultured MH - Chemokine CCL2/biosynthesis MH - Complement C5a/physiology MH - Fluorescent Antibody Technique MH - Glomerular Mesangium/*chemistry/cytology/metabolism MH - Humans MH - Platelet-Derived Growth Factor/biosynthesis MH - Receptor, Anaphylatoxin C5a MH - Receptors, Complement/*analysis/genetics/physiology EDAT- 1998/12/09 03:03 MHDA- 2001/03/28 10:01 CRDT- 1998/12/09 03:03 PHST- 1998/12/09 03:03 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1998/12/09 03:03 [entrez] AID - S0085-2538(15)30784-5 [pii] AID - 10.1046/j.1523-1755.1998.00155.x [doi] PST - ppublish SO - Kidney Int. 1998 Nov;54(5):1542-9. doi: 10.1046/j.1523-1755.1998.00155.x.