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PMID: 20395417 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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.

Blood ·Vol. 116 ·No. 6 ·2010-08-12 ·Pages 915-25

Boscacci RT, Pfeiffer F, Gollmer K, Sevilla AI, Martin AM, Soriano SF, Natale D, Henrickson S, von Andrian UH, Fukui Y, Mellado M, Deutsch U, Engelhardt B, Stein JV

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.

MeSH Terms
Animals Antigens, CD Cell Adhesion/immunology Cell Adhesion Molecules/genetics,metabolism Cell Movement/immunology Female Intercellular Adhesion Molecule-1/genetics,metabolism Lymph Nodes/blood supply,cytology Lymphocyte Count Lymphocytes/cytology,metabolism Male Mice Mice, Inbred C57BL Mice, Mutant Strains Microcirculation/immunology Stress, Mechanical Vascular Cell Adhesion Molecule-1/metabolism
Chemicals
Antigens, CD Cell Adhesion Molecules ICAM-2 protein, mouse Icam1 protein, mouse Vascular Cell Adhesion Molecule-1 Intercellular Adhesion Molecule-1
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Boscacci Rémy T
Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern, Switzerland.
Pfeiffer Friederike
Gollmer Kathrin
Sevilla Ana Isabel Checa
Martin Ana Maria
Soriano Silvia Fernandez
Natale Daniela
Henrickson Sarah
von Andrian Ulrich H
Fukui Yoshinori
Mellado Mario
Deutsch Urban
Engelhardt Britta
Stein Jens V
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
1528-0020
DOI
10.1182/blood-2009-11-254334
Published
2010-08-12
Epub
2010-00-15
Pages
915-25
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC3324225
Subset
IM
Grants
NIAID NIH HHS · R01 AI069259 · United States
NIAID NIH HHS · R01 AI072252 · United States
External Links
PubMed source DOI: 10.1182/blood-2009-11-254334 PMC Full Text View journal details
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