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

• Published in: Blood 2010-08, Vol.116 (6), p.915-925
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD; Cell Adhesion - immunology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Movement - immunology; Female; Immunobiology; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Lymph Nodes - blood supply; Lymph Nodes - cytology; Lymphocyte Count; Lymphocytes - cytology; Lymphocytes - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microcirculation - immunology; Stress, Mechanical; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2009-11-254334

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). Postarrest 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 α4-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.