scholarly journals 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 ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 915-925 ◽  
Author(s):  
Rémy T. Boscacci ◽  
Friederike Pfeiffer ◽  
Kathrin Gollmer ◽  
Ana Isabel Checa Sevilla ◽  
Ana Maria Martin ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
The Individual ◽  
Cell Adhesion Molecule 1

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). 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.

CXCL13 is an arrest chemokine for B cells in high endothelial venules

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2613-2618 ◽  
Author(s):  
Naotoshi Kanemitsu ◽  
Yukihiko Ebisuno ◽  
Toshiyuki Tanaka ◽  
Kazuhiro Otani ◽  
Haruko Hayasaka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
B Cell ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
High Endothelial Venules ◽  
Guanosine Triphosphatase ◽  
Cell Adhesion Molecule 1

Abstract Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13–/– mice and that B-cell adhesion is substantially restored in CXCL13–/– HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating α4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.

scholarly journals Local adiponectin treatment reduces atherosclerotic plaque size in rabbits

2007 ◽  
Vol 193 (1) ◽  
pp. 137-145 ◽  
Author(s):  
Chang-Jiang Li ◽  
Hui-Wen Sun ◽  
Fa-Liang Zhu ◽  
Liang Chen ◽  
Yuan-Yuan Rong ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Vascular Cell Adhesion ◽  
Intercellular Adhesion Molecule 1 ◽  
Plaque Area ◽  
Vascular Walls ◽  
Cell Adhesion Molecule 1

In this study, we investigated the in vivo role of adiponectin, an adipocytokine, on the development of atherosclerosis in rabbits mainly using adenovirus expressing adiponectin gene (Ad-APN) and intravascular ultrasonography. Serum adiponectin concentrations in rabbits after Ad-APN local transfer to abdominal aortas increased about nine times as much as those before transfer (P < 0.01), about ten times as much as the levels of endogenous adiponectin in adenovirus expressing β-galactosidase gene (Ad-β gal) treated rabbits (P < 0.01), and about four times as much as those in the aorta of non-injured rabbits on a normal cholesterol diet (P < 0.01). Ultrasonography revealed a significantly reduced atherosclerotic plaque area in abdominal aortas of rabbits infected through intima with Ad-APN, by 35.2% compared with the area before treatment (P < 0.01), and by 35.8% compared with that in Ad-β gal-treated rabbits (P < 0.01). In rabbits infected through adventitia, Ad-APN treatment reduced plaque area by 28.9% as compared with the area before treatment (P < 0.01) and 25.6% compared with that in Ad-β gal-treated rabbits (P < 0.01). Adiponectin significantly suppressed the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1) by 18.5% through intima transfer (P < 0.05) and 26.9% through adventitia transfer (P < 0.01), and intercellular adhesion molecule-1 (ICAM-1) by 40.7% through intima transfer (P < 0.01), and 30.7% through adventitia transfer (P < 0.01). However, adiponectin had no effect on the expression of types I and III collagen. These results suggest that local adiponectin treatment suppresses the development of atherosclerosis in vivo in part by attenuating the expression of VCAM-1 and ICAM-1 in vascular walls.

CYP450 dietary inhibitors attenuate TNF-α-stimulated endothelial molecule expression and leukocyte adhesion

2004 ◽  
Vol 286 (4) ◽  
pp. C931-C939 ◽  
Author(s):  
Makoto Sasaki ◽  
John W. Elrod ◽  
Paul Jordan ◽  
Makoto Itoh ◽  
Takashi Joh ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Adhesion ◽  
Tnf Α ◽  
Enhanced Expression ◽  
Cell Adhesion Molecule 1

Enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and other endothelial cell adhesion molecules (ECAMs) are associated with the onset and progression of inflammatory bowel disease (IBD). We show in this study that two cytochrome P-450 (CYP450) inhibitors from Citrus paradis (grapefruit), bergamottin, and 6′,7′-dihydroxybergamottin (DHB) block tumor necrosis factor (TNF)-α-stimulated expression of MAdCAM-1 in cultured endothelial cells and also reduce α4β7-dependent lymphocyte adhesion. Bergamottin (20–50 μM) or DHB (10–30 μM) pretreatment dose-dependently reduced TNF-α-mediated expression of MAdCAM-1 and lymphocyte adhesion. Bergamottin and DHB also prevented expression of two other ECAMs, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (but not E-selectin). SKF-525a, a specific CYP450 inhibitor, also blocked the expression of MAdCAM-1 mediated by TNF-α. Similar to SKF-525a (20 μM), bergamottin (20 μM) and DHB (20 μM) directly inhibited the activity of CYP450 3A4. These results suggest that natural CYP450 inhibitors may be effective in reducing ECAM expression and leukocyte adhesion and therefore be useful in the clinical treatment of inflammatory states like IBD.

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