Gene Expression Profiling of Mucosal Addressin Cell Adhesion Molecule-1+ High Endothelial Venule Cells (HEV) and Identification of a Leucine-Rich HEV Glycoprotein as a HEV Marker

Saito, Koichi; Tanaka, Toshiyuki; Kanda, Hidenobu; Ebisuno, Yukihiko; Izawa, Dai; Kawamoto, Shoko; Okubo, Kosaku; Miyasaka, Masayuki

doi:10.4049/jimmunol.168.3.1050

Cited by 62 publications

(61 citation statements)

References 46 publications

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“…TGF-β was reported to increase granulocyte/macrophage-colony stimulating factor (GM-CSF)-driven granulocyte differentiation, which was postulated to occur via increased surface expression of the GM-CSF receptor induced by TGF-β [29]. Recently, Saito et al reported isolation of LRG from high endothelial venule cells and proposed a role for LRG in adhesive interactions between lymphocytes and the endothelium [30]. They also reported that LRG immobilized on plastic wells could bind to TGF-β in vitro.…”

Section: Discussionmentioning

confidence: 99%

LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation

Druhan

Hunter

et al. 2008

Journal of Leukocyte Biology

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Expression of leucine-rich alpha-2 glycoprotein (LRG), a member of the leucine-rich repeat family of proteins, was recently shown to be upregulated during neutrophil differentiation. Its precise role in granulopoiesis, however, remains unknown. In this paper, we show that the transcription factors PU.1 and C/EBPε that regulate the expression of multiple myeloid-specific genes also bind to the LRG promoter. We also demonstrate that LRG localizes to the same cytoplasmic compartment as myeloperoxidase and that G-CSF treatment of the 32Dcl3 myeloid cell line induces nuclear translocation of LRG. Stable transfection of LRG into 32Dcl3 cells resulted in accelerated G-CSFmediated neutrophil differentiation and induction of CD11b expression. In contrast, constitutive expression of LRG in 32Dwt18 cells expressing a chimeric Epo/G-CSF receptor consisting of the Epo receptor extracellular domain fused to the G-CSF receptor transmembrane and cytoplasmic domains failed to induce accelerated neutrophil differentiation and CD11b expression in response to Epo stimulation. LRG-mediated accelerated differentiation and CD11b expression were found to correlate with an increased level of phospho-Stat3 but not with PU.1 or p27 kip1 levels. Hence, similar to other genes involved in neutrophil differentiation, the expression of LRG also appears to be regulated by PU.1 and C/EBPε. Collectively, these findings suggest a role for LRG in modulating neutrophil differentiation and expression of CD11b via non-redundant G-CSF receptor signals.

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Section: Discussionmentioning

confidence: 99%

LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation

Druhan

Hunter

et al. 2008

Journal of Leukocyte Biology

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“…8,9 Tissue-specific and vessel type-specific differences in ECs have also been detected at the transcriptional level by subtractive hybridization technologies 11,12 or gene expression profiling. [13][14][15] For instance, several tumor-specific EC molecules were identified by comparing gene expression patterns of ECs freshly isolated from blood vessels of normal or malignant colorectal tissue. 14 Although the molecular diversity of ECs is now clearly established, the origin of this heterogeneity remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment

Lacorre

Bækkevold

Garrido

et al. 2004

Blood

163

123

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Endothelial cells display remarkable heterogeneity in different organs and vascular beds. Although many studies suggest that tissues "speak" to endothelial cells, endothelial cell diversity remains poorly characterized at the molecular level. Here, we describe a novel strategy to characterize tissue-specific endothelial cell phenotypes and to identify endothelial cell genes that are under the control of the local microenvironment. By comparing postcapillary high endothelial venule endothelial cells (HEVECs), freshly isolated from human tonsils without any cell culture step, with HEVECs cultured for 2 days, we found that HEVECs rapidly lost their specialized characteristics when isolated from the lymphoid tissue microenvironment. Striking changes occurred as early as after 48 hours, with complete loss of the postcapillary venule-specific Duffy antigen receptor for chemokines (DARCs) and the HEV-specific fucosyltransferase Fuc-TVII. DNA microarray analysis identified several other candidate HEV genes that were rapidly down-regulated ex vivo, including type XV collagen, which we characterized as a novel, abundant HEV transcript in situ. Together, our results demonstrate that blood vessel typespecific and tissue-specific characteristics of endothelial cells are under the control of their microenvironment. Therefore, even short-term primary cultures of human endothelial cells may not adequately mimic the differentiated endothelial cell phenotypes existing in vivo. IntroductionAlthough all vascular endothelial cells (ECs) share certain common functions, it has become clear that considerable structural and functional heterogeneity exists along the length of the vascular tree and in the microvascular beds of various organs. [1][2][3][4][5][6][7] ECs either form a tight continuous monolayer in organs, where they render important barrier functions, such as in the brain (blood-brain barrier), or they form a discontinuous layer with intercellular gaps or fenestrations in organs, where the rapid exchange of fluid, particles, and cells is needed, such as in the kidney, spleen, and bone marrow. 1,6 EC diversity is also reflected at the molecular level, by vessel size-specific, tissue-specific and even disease-specific differences. 2,5,6 For instance, several organ-and tissue-specific EC receptors, called vascular addresses 8 or vascular signatures, 9 have recently been identified with in vivo phage display. 5,10 These vascular addresses may turn out to be useful for targeting therapies to blood vessels in various tissues or tumors. 8,9 Tissue-specific and vessel type-specific differences in ECs have also been detected at the transcriptional level by subtractive hybridization technologies 11,12 or gene expression profiling. [13][14][15] For instance, several tumor-specific EC molecules were identified by comparing gene expression patterns of ECs freshly isolated from blood vessels of normal or malignant colorectal tissue. 14 Although the molecular diversity of ECs is now clearly established, the origin of this heterogeneity re...

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“…While looking for genes specifically expressed in HEVs (11,12) we noticed that transcripts for a B cell chemokine CXCL13/ BLC were found in low abundance in cDNA libraries that we generated from PNAd ϩ HEVs and MAdCAM-1 ϩ HEVs. Therefore, we performed immunohistochemical analyses to examine whether CXCL13 is expressed in HEVs at the protein level.…”

Section: Cxcl13 Is Expressed In the Majority Of Hevsmentioning

confidence: 99%

“…Biotinylated anti-mouse CCL19, anti-mouse CCL21 and anti-mouse CXCL12 Abs were obtained from DAKO (Glostrup, Denmark), PeproTech (Rocky Hill, NJ) and Santa Cruz Biotechnology, respectively. MECA-79 (anti-peripheral node addressin (PNAd)) and MECA-367 (anti-mucosal addressin cell adhesion molecule (MAdCAM)-1) were kindly provided by Dr. E. C. Butcher (Stanford University, Stanford, CA) and used as described (11,12). Biotin-conjugated mAbs to CD3, B220, and CD11b were from BD PharMingen (San Diego, CA).…”

Section: Antibodiesmentioning

confidence: 99%

Cutting Edge: The B Cell Chemokine CXC Chemokine Ligand 13/B Lymphocyte Chemoattractant Is Expressed in the High Endothelial Venules of Lymph Nodes and Peyer’s Patches and Affects B Cell Trafficking Across High Endothelial Venules

Ebisuno

Tanaka

Kanemitsu

et al. 2003

The Journal of Immunology

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While CCR7 ligands direct T cell trafficking into lymph nodes (LNs) and Peyer’s patches (PPs), chemokines that regulate B cell trafficking across high endothelial venules (HEVs) remain to be fully elucidated. Here we report that CXC chemokine ligand (CXCL)13 (B lymphocyte chemoattractant) is detected immunohistologically in the majority of HEVs in LNs and PPs of nonimmunized mice. Systemically administered anti-CXCL13 Ab bound to the surface of ∼50% of HEVs in LNs and PPs, but not to other types of blood vessels, indicating that CXCL13 is expressed in the HEV lumen. In CXCL13-null mice, B cells rarely adhered to PP HEVs, whereas T cells did efficiently. Superfusion of CXCL13-null PPs with CXCL13 restored the luminal presentation of CXCL13 and also B cell arrest in PP HEVs at least partially. Collectively, these results indicate that CXCL13 expressed in the HEV lumen plays a crucial role in B cell trafficking into secondary lymphoid tissues such as PPs.

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Gene Expression Profiling of Mucosal Addressin Cell Adhesion Molecule-1+ High Endothelial Venule Cells (HEV) and Identification of a Leucine-Rich HEV Glycoprotein as a HEV Marker

Cited by 62 publications

References 46 publications

LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation

LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C/EBPε that modulate neutrophil activation

Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment

Cutting Edge: The B Cell Chemokine CXC Chemokine Ligand 13/B Lymphocyte Chemoattractant Is Expressed in the High Endothelial Venules of Lymph Nodes and Peyer’s Patches and Affects B Cell Trafficking Across High Endothelial Venules

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