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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.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author Boscacci Rémy T, 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,
Project Examining the function of lymphoid organ structure during antiviral immune responses using microscopic and mesoscopic imaging
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Original article (peer-reviewed)

Journal Blood
Volume (Issue) 116(6)
Page(s) 915 - 25
Title of proceedings Blood
DOI 10.1182/blood-2009-11-254334

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.
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