title: Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing.
abstract: Although it is well established that stromal intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule-1 (VCAM-1) mediate lymphocyte recruitment into peripheral lymph nodes (PLNs), their precise contributions to the individual steps of the lymphocyte homing cascade are not known. Here, we provide in vivo evidence for a selective function for ICAM-1 > ICAM-2 > VCAM-1 in lymphocyte arrest within noninflamed PLN microvessels. Blocking all 3 CAMs completely inhibited lymphocyte adhesion within PLN high endothelial venules (HEVs). Post-arrest extravasation of T cells was a 3-step process, with optional ICAM-1-dependent intraluminal crawling followed by rapid ICAM-1- or ICAM-2-independent diapedesis and perivascular trapping. Parenchymal motility of lymphocytes was modestly reduced in the absence of ICAM-1, while ICAM-2 and alpha4-integrin ligands were not required for B-cell motility within follicles. Our findings highlight nonredundant functions for stromal Ig family CAMs in shear-resistant lymphocyte adhesion in steady-state HEVs, a unique role for ICAM-1 in intraluminal lymphocyte crawling but redundant roles for ICAM-1 and ICAM-2 in lymphocyte diapedesis and interstitial motility.
authors.affiliation: Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern, Switzerland.
authors.forename: Rémy T
authors.initials: RT
authors.lastname: Boscacci
authors.forename: Friederike
authors.initials: F
authors.lastname: Pfeiffer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gollmer
authors.forename: Ana Isabel Checa
authors.initials: AI
authors.lastname: Sevilla
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martin
authors.forename: Silvia Fernandez
authors.initials: SF
authors.lastname: Soriano
authors.forename: Daniela
authors.initials: D
authors.lastname: Natale
authors.forename: Sarah
authors.initials: S
authors.lastname: Henrickson
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
mesh_terms: D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000098:blood supply / Q000166:cytology*; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008833:Microcirculation / Q000276:immunology; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C480027:ICAM-2 protein, mouse; C090509:Icam1 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
references.citation: Eur J Immunol. 2004 Nov;34(11):2955-63
references.pmid: 15376193
references.citation: Cell Tissue Res. 1995 Jan;279(1):47-54
references.pmid: 7895264
references.citation: PLoS Biol. 2005 Apr;3(4):e113
references.pmid: 15799695
references.citation: Lab Invest. 1999 Mar;79(3):327-36
references.pmid: 10092069
references.citation: J Exp Med. 2007 Mar 19;204(3):497-510
references.pmid: 17325199
references.citation: Nat Immunol. 2007 Oct;8(10):1076-85
references.pmid: 17721537
references.citation: Microcirculation. 1996 Sep;3(3):287-300
references.pmid: 8930886
references.citation: J Immunol. 2008 Sep 15;181(6):3947-54
references.pmid: 18768849
references.citation: Immunity. 1999 Jan;10(1):9-19
references.pmid: 10023766
references.citation: J Exp Med. 2001 May 7;193(9):1105-12
references.pmid: 11342595
references.citation: Nat Rev Immunol. 2003 Nov;3(11):867-78
references.pmid: 14668803
references.citation: Int Immunol. 2004 Aug;16(8):1133-42
references.pmid: 15237106
references.citation: Nature. 2004 Jan 8;427(6970):154-9
references.pmid: 14712275
references.citation: J Exp Med. 1999 May 3;189(9):1467-78
references.pmid: 10224287
references.citation: Blood. 2006 Oct 1;108(7):2150-8
references.pmid: 16772603
references.citation: J Cell Biol. 2002 Jun 24;157(7):1233-45
references.pmid: 12082081
references.citation: Nature. 2008 May 1;453(7191):51-5
references.pmid: 18451854
references.citation: Immunity. 2000 Dec;13(6):759-69
references.pmid: 11163192
references.citation: Immunity. 2009 Mar 20;30(3):384-96
references.pmid: 19268609
references.citation: Immunity. 2006 Dec;25(6):989-1001
references.pmid: 17112751
references.citation: Nat Immunol. 2007 Nov;8(11):1255-65
references.pmid: 17893676
references.citation: J Immunol. 2003 Sep 1;171(5):2588-93
references.pmid: 12928410
references.citation: J Exp Med. 2003 Feb 3;197(3):353-61
references.pmid: 12566419
references.citation: Blood. 2009 Jun 11;113(24):6246-57
references.pmid: 19211506
references.citation: Nat Rev Immunol. 2007 Jun;7(6):467-77
references.pmid: 17525755
references.citation: Nat Immunol. 2008 Sep;9(9):960-9
references.pmid: 18711433
references.citation: Nat Immunol. 2005 May;6(5):497-506
references.pmid: 15834409
references.citation: Nat Rev Immunol. 2004 May;4(5):360-70
references.pmid: 15122201
references.citation: J Immunol. 2009 Jul 1;183(1):359-69
references.pmid: 19542447
references.citation: Nature. 2001 Aug 23;412(6849):826-31
references.pmid: 11518968
references.citation: Annu Rev Immunol. 2005;23:127-59
references.pmid: 15771568
references.citation: Nat Rev Immunol. 2008 Oct;8(10):764-75
references.pmid: 18825130
references.citation: Curr Opin Cell Biol. 2008 Oct;20(5):533-40
references.pmid: 18595683
references.citation: J Exp Med. 2006 Nov 27;203(12):2569-75
references.pmid: 17116736
references.citation: Immunity. 2004 Sep;21(3):429-41
references.pmid: 15357953
references.citation: J Exp Med. 2003 Sep 1;198(5):715-24
references.pmid: 12953093
references.citation: J Immunol. 1997 Jun 15;158(12):5584-8
references.pmid: 9190904
references.citation: Eur J Immunol. 2008 Aug;38(8):2142-55
references.pmid: 18629939
references.citation: Genesis. 2009 Apr;47(4):281-7
references.pmid: 19263498
references.citation: J Immunol. 1988 Feb 1;140(3):693-9
references.pmid: 3276776
references.citation: J Exp Med. 2000 Jan 3;191(1):61-76
references.pmid: 10620605
references.citation: J Exp Med. 1998 Jan 19;187(2):205-16
references.pmid: 9432978
references.citation: Science. 2007 Aug 3;317(5838):666-70
references.pmid: 17673663
references.citation: Immunol Rev. 2008 Feb;221:26-43
references.pmid: 18275473
references.citation: Immunity. 2007 Jan;26(1):17-27
references.pmid: 17241958
references.citation: Blood. 2003 Nov 15;102(10):3675-83
references.pmid: 12893765
references.citation: J Exp Med. 1994 Jul 1;180(1):95-109
references.pmid: 7911822
references.citation: J Immunol. 2008 Nov 1;181(9):6189-200
references.pmid: 18941209
references.citation: J Cell Biol. 2004 Oct 25;167(2):377-88
references.pmid: 15504916