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

Boscacci, Rémy T; Pfeiffer, Friederike; Gollmer, Kathrin; Checa Sevilla, Ana Isabel; 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 (2010). 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, 116(6), pp. 915-25. Washington, D.C.: American Society of Hematology 10.1182/blood-2009-11-254334

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute 04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
UniBE Contributor:	Gollmer, Kathrin, Martin, Andrea, Natale, Daniela, Deutsch, Urban, Engelhardt, Britta, Stein, Jens Volker
ISSN:	0006-4971
Publisher:	American Society of Hematology
Language:	English
Submitter:	Jeannie Wurz
Date Deposited:	04 Oct 2013 14:08
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1182/blood-2009-11-254334
PubMed ID:	20395417
Web of Science ID:	000280881700013
URI:	https://boris.unibe.ch/id/eprint/333 (FactScience: 197606)