title: Interference with glycosaminoglycan-chemokine interactions with a probe to alter leukocyte recruitment and inflammation in vivo.
abstract: In vivo leukocyte recruitment is not fully understood and may result from interactions of chemokines with glycosaminoglycans/GAGs. We previously showed that chlorite-oxidized oxyamylose/COAM binds the neutrophil chemokine GCP-2/CXCL6. Here, mouse chemokine binding by COAM was studied systematically and binding affinities of chemokines to COAM versus GAGs were compared. COAM and heparan sulphate bound the mouse CXC chemokines KC/CXCL1, MIP-2/CXCL2, IP-10/CXCL10 and I-TAC/CXCL11 and the CC chemokine RANTES/CCL5 with affinities in the nanomolar range, whereas no binding interactions were observed for mouse MCP-1/CCL2, MIP-1α/CCL3 and MIP-1β/CCL4. The affinities of COAM-interacting chemokines were similar to or higher than those observed for heparan sulphate. Although COAM did not display chemotactic activity by itself, its co-administration with mouse GCP-2/CXCL6 and MIP-2/CXCL2 or its binding of endogenous chemokines resulted in fast and cooperative peritoneal neutrophil recruitment and in extravasation into the cremaster muscle in vivo. These local GAG mimetic features by COAM within tissues superseded systemic effects and were sufficient and applicable to reduce LPS-induced liver-specific neutrophil recruitment and activation. COAM mimics glycosaminoglycans and is a nontoxic probe for the study of leukocyte recruitment and inflammation in vivo.
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Ulrika S
authors.initials: US
authors.lastname: Pettersson
authors.affiliation: Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Hoorelbeke
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; Jagiellonian University, Krakow, Poland; Snyder Institute for Chronic Diseases, and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kolaczkowska
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Schelfhout
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Martens
authors.affiliation: Snyder Institute for Chronic Diseases, and Department of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Phillipson
authors.affiliation: Laboratory of Immunobiology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000595:Amino Acid Sequence; D000688:Amylose / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D065206:Extracellular Traps / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007274:Injections, Intraperitoneal; D007526:Isoelectric Point; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D020349:Surface Plasmon Resonance
chemical_list: D000688:Amylose; D018925:Chemokines; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008070:Lipopolysaccharides; C002668:oxyamylose
references.citation: Clin Exp Allergy. 1998 May;28(5):616-24
references.pmid: 9645599
references.citation: Nat Immunol. 2005 Sep;6(9):902-10
references.pmid: 16056228
references.citation: Biochem Pharmacol. 2008 Oct 1;76(7):831-40
references.pmid: 18703022
references.citation: Blood. 2010 Sep 16;116(11):1924-31
references.pmid: 20530797
references.citation: J Biol Chem. 2010 Mar 19;285(12):8782-92
references.pmid: 20097750
references.citation: J Immunol. 2008 Mar 15;180(6):4308-15
references.pmid: 18322244
references.citation: Immunity. 2000 Feb;12(2):121-7
references.pmid: 10714678
references.citation: J Biol Chem. 2004 May 21;279(21):22294-305
references.pmid: 15033992
references.citation: N Engl J Med. 1998 Feb 12;338(7):436-45
references.pmid: 9459648
references.citation: J Biol Chem. 2004 Oct 15;279(42):43854-60
references.pmid: 15292258
references.citation: Nat Immunol. 2001 Feb;2(2):123-8
references.pmid: 11175804
references.citation: J Biol Chem. 2007 May 18;282(20):15238-47
references.pmid: 17384413
references.citation: Cell Host Microbe. 2012 Sep 13;12(3):324-33
references.pmid: 22980329
references.citation: Cytokine Growth Factor Rev. 2005 Dec;16(6):625-36
references.pmid: 15990353
references.citation: Cytokine Growth Factor Rev. 2005 Dec;16(6):593-609
references.pmid: 16046180
references.citation: J Leukoc Biol. 2009 Sep;86(3):671-80
references.pmid: 19451399
references.citation: J Immunol. 2001 Dec 1;167(11):6552-8
references.pmid: 11714824
references.citation: Blood. 2008 Jan 1;111(1):42-9
references.pmid: 17928531
references.citation: Int J Cancer. 2012 Aug 15;131(4):E425-36
references.pmid: 21953247
references.citation: J Immunol. 1999 Dec 1;163(11):6155-63
references.pmid: 10570306
references.citation: J Neuroinflammation. 2012 Oct 25;9:243
references.pmid: 23095573
references.citation: J Immunol. 2010 Mar 1;184(5):2677-85
references.pmid: 20124102
references.citation: J Leukoc Biol. 2010 Nov;88(5):1017-29
references.pmid: 20709940
references.citation: J Virol. 1970 Mar;5(3):313-20
references.pmid: 4314553
references.citation: Biochemistry. 1999 Sep 28;38(39):12959-68
references.pmid: 10504268
references.citation: Cell Host Microbe. 2013 Feb 13;13(2):169-80
references.pmid: 23414757
references.citation: J Exp Med. 2006 Nov 27;203(12):2569-75
references.pmid: 17116736
references.citation: Blood. 1997 Aug 1;90(3):909-28
references.pmid: 9242519
references.citation: Immunol Rev. 2000 Oct;177:195-203
references.pmid: 11138776
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1885-90
references.pmid: 12571364
references.citation: Am J Pathol. 2001 Apr;158(4):1441-50
references.pmid: 11290562
references.citation: Clin Exp Immunol. 1998 May;112(2):270-5
references.pmid: 9649190
references.citation: J Immunol. 1996 Aug 15;157(4):1736-43
references.pmid: 8759763
references.citation: Eur J Immunol. 2005 May;35(5):1583-91
references.pmid: 15827963
references.citation: Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7158-62
references.pmid: 8346230