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Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell lines

På svenska

Author

  • Kay Johswich
  • Myriam Martin
  • Jessica Thalmann
  • Claudia Rheinheimer
  • Peter N Monk
  • Andreas Klos

Summary, in English

During complement activation the pro-inflammatory anaphylatoxins C3a and C5a are generated, which interact with the C3a receptor and C5a receptor (CD88), respectively. C5a and its degradation product C5a-des-Arg(74) also bind to the C5a receptor-like 2 (C5L2). C3a and C3a-des-Arg(77), also called acylation-stimulating protein, augment triglyceride synthesis and glucose uptake in adipocytes and skin fibroblasts. Based on data obtained using transfected HEK293 and RBL cells, C5L2 is additionally proposed as a functional receptor for C3a and C3a-des-Arg(77). Here we use (125)I-ligand binding assays and flow cytometry with fluorescently labeled ligands to demonstrate that neither C3a nor C3a-des-Arg(77) binds to C5L2. C5L2 expression and its regulation are investigated on various cell lines by a novel C5L2-restricted binding assay and quantitative real time PCR. Dibutyryl cAMP and interferon-gamma induce up-regulation of this receptor on myeloblastic cell lines (U937 and HL-60), whereas tumor necrosis factor-alpha (TNF-alpha) has no effect. In contrast, epithelial HeLa cells are found to constitutively express C5L2 but not the C5a receptor. In HeLa cells, interferon-gamma and TNF-alpha drastically reduce C5L2 expression. No C5a-dependent Ca(2+) signaling is observed even in these cells endogenously expressing C5L2. Taken together, C5L2 is not a receptor for C3a or C3a-des-Arg(77). Thus, this receptor is unlikely to be directly involved in lipid metabolism. Instead, the identification of stimuli modifying C5L2 expression indicates that C5L2 is a highly regulated scavenger receptor for C5a and C5a-des-Arg(74).

Publishing year

2006

Language

English

Pages

39088-39095

Publication/Series

Journal of Biological Chemistry

Volume

281

Issue

51

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Other Basic Medicine

Status

Published

Research group

  • Protein Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 1083-351X