title: Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis.
abstract: Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell-expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated mast cell-dependent passive cutaneous anaphylaxis but can enhance the tissue swelling and leukocyte infiltrates associated with such reactions in mice. We further identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. In contrast to other "silent" or professional chemokine interreceptors, chemerin binding does not trigger ligand internalization. Rather, CCRL2 is able to bind the chemoattractant and increase local concentrations of bioactive chemerin, thus providing a link between CCRL2 expression and inflammation via the cell-signaling chemerin receptor CMKLR1.
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. bazabel@alum.mit.edu
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Luis
authors.initials: L
authors.lastname: Zúñiga
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Kim
authors.forename: Takao
authors.initials: T
authors.lastname: Ohyama
authors.forename: Carsten
authors.initials: C
authors.lastname: Alt
authors.forename: Junliang
authors.initials: J
authors.lastname: Pan
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Dulce
authors.initials: D
authors.lastname: Soler
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Song
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology*; D054388:Receptors, CCR / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C487531:CCRL2 protein, human; C111851:Ccrl2 protein, mouse; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D007073:Immunoglobulin E
references.citation: J Immunol. 2006 Apr 1;176(7):4102-12
references.pmid: 16547246
references.citation: Int Arch Allergy Immunol. 2004 Sep;135(1):62-72
references.pmid: 15316148
references.citation: Mol Biol Cell. 2004 May;15(5):2492-508
references.pmid: 15004236
references.citation: J Immunol. 2001 Apr 15;166(8):5000-7
references.pmid: 11290780
references.citation: Int Immunol. 2004 May;16(5):685-95
references.pmid: 15096484
references.citation: Proc Natl Acad Sci U S A. 2005 May 3;102(18):6467-72
references.pmid: 15840716
references.citation: Adv Protein Chem. 2004;68:351-91
references.pmid: 15500866
references.citation: J Biol Chem. 2005 Oct 14;280(41):34661-6
references.pmid: 16096270
references.citation: J Exp Med. 1996 Jun 1;183(6):2437-48
references.pmid: 8676064
references.citation: FEBS Lett. 1998 Apr 3;425(3):490-4
references.pmid: 9563519
references.citation: J Immunol. 2005 Apr 1;174(7):3880-90
references.pmid: 15778342
references.citation: Biochem Biophys Res Commun. 1998 Feb 4;243(1):264-8
references.pmid: 9473515
references.citation: Bioessays. 2007 Mar;29(3):237-47
references.pmid: 17295321
references.citation: J Immunol. 1988 Apr 1;140(7):2356-60
references.pmid: 3280681
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:43-66
references.pmid: 14744238
references.citation: Glia. 2003 Mar;41(4):327-36
references.pmid: 12555200
references.citation: Arthritis Rheum. 2004 Jun;50(6):1806-14
references.pmid: 15188357
references.citation: Nat Immunol. 2005 Feb;6(2):135-42
references.pmid: 15662442
references.citation: J Immunol. 2006 Jan 1;176(1):401-15
references.pmid: 16365434
references.citation: Exp Hematol. 2006 Aug;34(8):1021-32
references.pmid: 16863908
references.citation: FEBS Lett. 2003 Dec 18;555(3):495-9
references.pmid: 14675762
references.citation: J Leukoc Biol. 2003 Aug;74(2):243-51
references.pmid: 12885941
references.citation: J Exp Med. 2003 Oct 6;198(7):977-85
references.pmid: 14530373
references.citation: Glia. 2004 Apr 1;46(1):84-94
references.pmid: 14999816
references.citation: J Clin Invest. 1993 Mar;91(3):1176-82
references.pmid: 8450046
references.citation: Nat Rev Immunol. 2006 Dec;6(12):907-18
references.pmid: 17124512
references.citation: Eur J Immunol. 2002 Feb;32(2):494-501
references.pmid: 11828366
references.citation: J Exp Med. 1997 Oct 20;186(8):1307-14
references.pmid: 9334370
references.citation: Blood. 2007 May 1;109(9):3625-32
references.pmid: 17202316
references.citation: Int Immunol. 2003 Oct;15(10):1219-27
references.pmid: 13679391
references.citation: J Immunol. 1980 Jun;124(6):2728-37
references.pmid: 7373045
references.citation: Blood. 1997 May 1;89(9):3077-91
references.pmid: 9129009
references.citation: Cell. 1997 Oct 31;91(3):385-95
references.pmid: 9363947
references.citation: J Immunol. 2005 Jul 1;175(1):487-93
references.pmid: 15972683
references.citation: J Exp Med. 1998 Apr 20;187(8):1235-47
references.pmid: 9547335
references.citation: Eur J Immunol. 2006 Jul;36(7):1659-61
references.pmid: 16791884
references.citation: Blood. 1992 Sep 15;80(6):1448-53
references.pmid: 1381627
references.citation: Eur J Immunol. 2006 Jul;36(7):1904-16
references.pmid: 16791897
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Biotechnol. 1991 Jun;19(1):35-47
references.pmid: 1369310
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Nov 25;811(2):217-23
references.pmid: 15522723
references.citation: J Clin Invest. 1991 Feb;87(2):446-53
references.pmid: 1991831
references.citation: J Immunol. 2003 May 15;170(10):5244-51
references.pmid: 12734373
references.citation: J Clin Invest. 1991 Oct;88(4):1362-9
references.pmid: 1918386
references.citation: J Histochem Cytochem. 2004 Mar;52(3):401-10
references.pmid: 14966207
references.citation: J Immunol. 2006 Feb 15;176(4):2238-48
references.pmid: 16455980
references.citation: Exp Hematol. 2006 Aug;34(8):1106-14
references.pmid: 16863918
references.citation: J Immunol. 2005 Jan 1;174(1):244-51
references.pmid: 15611246