Advanced

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

Johswich, Kay ; Martin, Myriam LU ; Thalmann, Jessica ; Rheinheimer, Claudia ; Monk, Peter N and Klos, Andreas (2006) In Journal of Biological Chemistry 281(51). p.39088-39095
Abstract
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... (More)
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). (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
51
pages
39088 - 39095
publisher
ASBMB
external identifiers
  • pmid:17068344
  • scopus:33846027130
ISSN
1083-351X
DOI
10.1074/jbc.M609734200
language
English
LU publication?
yes
id
79d9166d-bb6b-490f-a7ee-2113bfd01944 (old id 1136930)
date added to LUP
2016-04-01 11:45:23
date last changed
2020-09-16 01:45:14
@article{79d9166d-bb6b-490f-a7ee-2113bfd01944,
  abstract     = {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).},
  author       = {Johswich, Kay and Martin, Myriam and Thalmann, Jessica and Rheinheimer, Claudia and Monk, Peter N and Klos, Andreas},
  issn         = {1083-351X},
  language     = {eng},
  number       = {51},
  pages        = {39088--39095},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell lines},
  url          = {http://dx.doi.org/10.1074/jbc.M609734200},
  doi          = {10.1074/jbc.M609734200},
  volume       = {281},
  year         = {2006},
}