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https://www.readbyqxmd.com/read/28645652/androgen-inhibits-key-atherosclerotic-processes-by-directly-activating-adtrp-transcription
#1
Chunyan Luo, Elisabeth Pook, Bo Tang, Weiyi Zhang, Sisi Li, Kirsten Leineweber, Shing-Hu Cheung, Qiuyun Chen, Martin Bechem, Jing-Shan Hu, Volker Laux, Qing Kenneth Wang
Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. In this study, we identified the molecular mechanism by which androgen regulates ADTRP expression and tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#2
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#3
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28637894/deep-insight-into-neutrophil-trafficking-in-various-organs
#4
REVIEW
Young-Min Hyun, Chang-Won Hong
Neutrophils are professional phagocytes that constitute the first line of defense in humans. The primary function of neutrophils is to eliminate invading pathogens through oxidative and nonoxidative mechanisms. Because neutrophils rapidly migrate into inflammatory foci via diapedesis and chemotaxis, neutrophil recruitment has long been considered a hallmark of inflammation. Recent advances in intravital microscopic technologies using animal model systems have enabled researchers to directly visualize neutrophil trafficking...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#5
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28626344/increased-transendothelial-transport-of-ccl3-is-insufficient-to-drive-immune-cell-transmigration-through-the-blood-brain-barrier-under-inflammatory-conditions-in-vitro
#6
Maxime De Laere, Carmelita Sousa, Megha Meena, Roeland Buckinx, Jean-Pierre Timmermans, Zwi Berneman, Nathalie Cools
Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood-brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28600306/expression-of-lewis-a-glycans-on-polymorphonuclear-leukocytes-augments-function-by-increasing-transmigration
#7
Jennifer C Brazil, Ronen Sumagin, Sean R Stowell, Goo Lee, Nancy A Louis, Richard D Cummings, Charles A Parkos
PMN-expressed fucosylated glycans from the Lewis glycan family, including Lewis-x (Le(x)) and sialyl Lewis-x (sLe(x)), have previously been implicated in the regulation of important PMN functions, including selectin-mediated trafficking across vascular endothelium. Although glycans, such as Le(x) and sLe(x), which are based on the type 2 sequence (Galβ1-4GlcNAc-R), are abundant on PMNs, the presence of type 1 Galβ1-3GlcNAc-R glycans required for PMN expression of the closely related stereoisomer of Le(x), termed Lewis-A (Le(a)), has not, to our knowledge, been reported...
June 9, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#8
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28596573/fibroblast-growth-factor-23-weakens-chemotaxis-of-human-blood-neutrophils-in-microfluidic-devices
#9
Ke Yang, Hagit Peretz-Soroka, Jiandong Wu, Ling Zhu, Xueling Cui, Michael Zhang, Claudio Rigatto, Yong Liu, Francis Lin
Neutrophil trafficking in tissues critically regulates the body's immune response. Neutrophil migration can either play a protective role in host defense or cause health problems. Fibroblast growth factor 23 (FGF23) is a known biomarker for chronic kidney disease (CKD) and was recently shown to impair neutrophil arrest on endothelium and transendothelial migration. In the present study, we further examined the effect of FGF23 on human blood neutrophil chemotaxis using two new microfluidic devices. Our results showed that chemotaxis of FGF23 pre-treated neutrophils to a fMLP gradient, in the presence or absence of a uniform FGF23 background, is quantitatively lower compared to the control cells...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28596294/the-metalloproteinase-adam8-promotes-leukocyte-recruitment-in-vitro-and-in-acute-lung-inflammation
#10
Daniela Dreymueller, Jessica Pruessmeyer, Julian Schumacher, Sandra Fellendorf, Franz Martin Hess, Anke Seifert, Aaron Babendreyer, Joerg Walter Bartsch, Andreas Ludwig
Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28578388/antibody-blockade-of-clec12a-delays-eae-onset-and-attenuates-disease-severity-by-impairing-myeloid-cell-cns-infiltration-and-restoring-positive-immunity
#11
Divya Sagar, Narendra P Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M Andrews, Servio H Ramirez, Zafar K Khan, Pooja Jain
The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35-55-induced progressive, as well as PLP138-151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28559148/leukocyte-breaching-of-endothelial-barriers-the-actin-link
#12
REVIEW
Ronen Alon, Jaap D van Buul
Leukocyte transendothelial migration (TEM) takes place across micron-wide gaps in specific post-capillary venules generated by the transmigrating leukocyte. Because endothelial cells contain a dense cytoskeletal network, transmigrating leukocytes must overcome these mechanical barriers as they squeeze their nuclei through endothelial gaps and pores. Recent findings suggest that endothelial cells are not a passive barrier, and upon engagement by transmigrating leukocytes trigger extensive dynamic modifications of their actin cytoskeleton...
May 27, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28553955/deletion-of-adam-9-in-hgf-cdk4-mice-impairs-melanoma-development-and-metastasis
#13
N Giebeler, A Schönefuß, J Landsberg, T Tüting, C Mauch, P Zigrino
ADAM-9 is a metalloproteinase expressed in peritumoral areas by invading melanoma cells and by adjacent peritumoral stromal cells; however, its function in stromal and melanoma cells is not fully understood. To address this question in vivo in a spontaneous melanoma model, we deleted ADAM-9 in mice carrying the hepatocyte growth factor (Hgf) transgene and knock-in mutation Cdk4(R24C/R24C), demonstrated to spontaneously develop melanoma. Spontaneous melanoma arose less frequently in ADAM-9-deleted mice than in controls...
May 29, 2017: Oncogene
https://www.readbyqxmd.com/read/28551814/macrophage-derived-interleukin-1beta-promotes-human-breast-cancer-cell-migration-and-lymphatic-adhesion-in-vitro
#14
Sarah J Storr, Sabreena Safuan, Narmeen Ahmad, Mohammed El-Refaee, Andrew M Jackson, Stewart G Martin
Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0...
May 27, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28545889/car-a-key-regulator-of-adhesion-and-inflammation
#15
Elena Ortiz-Zapater, George Santis, Maddy Parsons
The coxsackie and adenovirus receptor (CAR) is a transmembrane receptor that plays a key role in controlling adhesion between adjacent epithelial cells. CAR is highly expressed in epithelial cells and was originally identified as a primary receptor for adenovirus cell binding. However, studies over the last 10 years have demonstrated that CAR plays a key role in co-ordinating cell-cell adhesion under homeostatic conditions including neuronal and cardiac development and cell junction stability; it has also been implicated in pathological states such as cancer growth and leukocyte transmigration during inflammation...
May 22, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28542193/an-agent-based-model-of-leukocyte-transendothelial-migration-during-atherogenesis
#16
Rita Bhui, Heather N Hayenga
A vast amount of work has been dedicated to the effects of hemodynamics and cytokines on leukocyte adhesion and trans-endothelial migration (TEM) and subsequent accumulation of leukocyte-derived foam cells in the artery wall. However, a comprehensive mechanobiological model to capture these spatiotemporal events and predict the growth and remodeling of an atherosclerotic artery is still lacking. Here, we present a multiscale model of leukocyte TEM and plaque evolution in the left anterior descending (LAD) coronary artery...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28537941/pathophysiology-of-anca-associated-vasculitis
#17
Turki Al-Hussain, Maged H Hussein, Walter Conca, Hadeel Al Mana, Mohammed Akhtar
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized as inflammation of small-sized to medium-sized blood vessels and encompasses several clinicopathologic entities including granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited ANCA-associated vasculitis. Over the past several decades, significant progress has been made in understanding the pathophysiology of ANCA-associated vasculitis. Although neutrophils contain a multitude of granular proteins, clinically significant autoantibodies are only recognized against myeloperoxidase and proteinase 3, both of which are present in the azurophilic granules...
July 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28533307/sox11-promotes-tumor-protective-microenvironment-interactions-through-cxcr4-and-fak-regulation-in-mantle-cell-lymphoma
#18
Patricia Balsas, Jara Palomero, Álvaro Eguileor, Marta Leonor Rodriguez, Maria Carmela Vegliante, Ester Planas-Rigol, Marta Sureda-Gómez, Maria C Cid, Elias Campo, Virginia Amador
SOX11 overexpression in Mantle Cell Lymphoma (MCL) has been associated with more aggresive behavior and worse outcome. However, SOX11 oncogenic pathways driving MCL tumor progression are poorly known. Here, we demonstrate that SOX11 binds to regulatory regions of two important genes for microenvironment-signals in cancer, (C-X-C motif) chemokine receptor 4 (CXCR4) and PTK2 (encoding for focal adhesion kinase (FAK)). Moreover, SOX11-positive xenograft and human primary MCL tumors overexpress cell migration and stromal stimulation gene signatures compared to their SOX11-negative counterparts...
May 22, 2017: Blood
https://www.readbyqxmd.com/read/28504320/photosensitization-priming-of-tumor-microenvironments-improves-delivery-of-nanotherapeutics-via-neutrophil-infiltration
#19
Dafeng Chu, Xinyue Dong, Qi Zhao, Jingkai Gu, Zhenjia Wang
Remodeling of tumor microenvironments enables enhanced delivery of nanoparticles (NPs). This study shows that direct priming of a tumor tissue using photosensitization rapidly activates neutrophil infiltration that mediates delivery of nanotherapeutics into the tumor. A drug delivery platform is comprised of NPs coated with anti-CD11b antibodies (Abs) that target activated neutrophils. Intravital microscopy demonstrates that the movement of anti-CD11b Abs-decorated NPs (NPs-CD11b) into the tumor is mediated by neutrophil infiltration induced by photosensitization (PS) because the systemic depletion of neutrophils completely abolishes the nanoparticle tumor deposition...
May 15, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28487567/a-robust-in-vitro-model-for-trans-lymphatic-endothelial-migration
#20
Yanbao Xiong, C Colin Brinkman, Konrad S Famulski, Emmanuel F Mongodin, Colin J Lord, Keli L Hippen, Bruce R Blazar, Jonathan S Bromberg
Trans-endothelial migration (TEM) is essential for leukocyte circulation. While much is known about trans-blood endothelial migration, far less is known about trans-lymphatic endothelial migration. We established an in vitro system to evaluate lymphatic TEM for various cell types across primary mouse and human lymphatic endothelial cells (LEC), and validated the model for the murine LEC cell line SVEC4-10. T cells exhibited enhanced unidirectional migration from the basal (abluminal) to the apical (luminal) surface across LEC, whereas for blood endothelial cells (BEC) they migrated similarly in both directions...
May 9, 2017: Scientific Reports
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