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https://www.readbyqxmd.com/read/29703483/the-role-of-podoplanin-in-cancer-associated-thrombosis
#1
Pegah Mir Seyed Nazari, Julia Riedl, Ingrid Pabinger, Cihan Ay
Venous thromboembolism (VTE) is a frequent and life-threatening complication in patients with cancer. The underlying mechanisms of cancer-associated VTE are still not completely understood. However, emerging studies indicate that the mechanisms differ across tumor types. A recent study revealed that in patients with brain tumors, podoplanin overexpression is strongly correlated with intratumoral thrombotic vessels, hypercoagulability and increased VTE risk. In vitro experiments demonstrated that platelet aggregation induced by human glioblastoma cells was highly podoplanin-dependent...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29702464/transforming-growth-factor-%C3%AE-1-impairs-lymph-node-homing-of-dendritic-cells-by-downregulating-c-type-lectin-receptor-2-expression
#2
Ravindra Gujar, Pradip Sen
Trafficking of dendritic cells (DCs) from peripheral tissues to draining lymph nodes is a prerequisite for induction of adaptive immunity. An immunosuppressive cytokine transforming growth factor (TGF)-β1, however, inhibits migration of DCs by downregulating the expression of chemokine receptor CCR-7. Whether TGF-β1 engages any other receptor to mediate this inhibitory effect is currently unknown. In this article, we report that TGF-β1 attenuated the lymph node homing ability of mouse DCs by reducing C-type lectin receptor-2 (CLEC-2) expression...
April 24, 2018: Cytokine
https://www.readbyqxmd.com/read/29695020/significant-hypo-responsiveness-to-gpvi-and-clec-2-agonists-in-pre-term-and-full-term-neonatal-platelets-and-following-immune-thrombocytopenia
#3
Alexander T Hardy, Verónica Palma-Barqueros, Stephanie K Watson, Jean-Daniel Malcor, Johannes A Eble, Elizabeth E Gardiner, José E Blanco, Rafael Guijarro-Campillo, Juan L Delgado, María L Lozano, Raúl Teruel-Montoya, Vicente Vicente, Steve P Watson, José Rivera, Francisca Ferrer-Marín
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation...
April 25, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29608407/epitope-mapping-of-monoclonal-antibody-pmab-48-against-dog-podoplanin
#4
Shinji Yamada, Mika K Kaneko, Shunsuke Itai, Yao-Wen Chang, Takuro Nakamura, Miyuki Yanaka, Satoshi Ogasawara, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Hiroyuki Harada, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells...
April 2, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29578204/differences-in-gene-expression-related-to-the-results-of-obesity-treatment-peak-oxygen-uptake-and-fatty-acid-metabolism-measured-in-a-cardiopulmonary-exercise-test
#5
Marta Gruchała-Niedoszytko, Pieter van der Vlies, Piotr Niedoszytko, Bahram Sanjabi, Marek Niedoszytko, Małgorzata Kaczkan, Magdalena Pieszko, Katarzyna Gierat-Haponiuk, Aleksandra Śliwińska, Dominika Szalewska, Sylwia Małgorzewicz
INTRODUCTION    The impact of obesity requires methods used on a large scale as  cardiopulmonary exercise test (CPET). The gene expression may explain CPET results on molecular level.   OBJECTIVES    The aim of the study was to compare gene expression in obesity,  differences related to the CPET results. PATIENTS AND METHODS    The study group consisted of 9 obese and 7 controls. The treatment consisted of diet, rehabilitation, behavioural therapy. Diet was based on the body composition analysed by bioelectrical impedance (BIA), resting metabolic rate, and subjective patients' preferences...
March 26, 2018: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/29488681/functional-characterization-of-recombinant-snake-venom-rhodocytin-rhodocytin-mutant-blocks-clec-2-podoplanin-dependent-platelet-aggregation-and-lung-metastasis
#6
T Sasaki, T Shirai, N Tsukiji, S Otake, S Tamura, J Ichikawa, M Osada, K Satoh, Y Ozaki, K Suzuki-Inoue
Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. SUMMARY: Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2)...
May 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29488279/origin-specific-adhesive-interactions-of-mesenchymal-stem-cells-with-platelets-influence-their-behavior-after-infusion
#7
Lozan Sheriff, Asma Alanazi, Lewis S C Ward, Carl Ward, Hafsa Munir, Julie Rayes, Mohammed Alassiri, Steve P Watson, Phil N Newsome, G E Rainger, Neena Kalia, Jon Frampton, Helen M McGettrick, Gerard B Nash
We investigated the adhesive behavior of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow MSC (BMMSC) or umbilical cord MSC (UCMSC) adhered efficiently from flow to the matrix proteins, collagen, or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer...
February 28, 2018: Stem Cells
https://www.readbyqxmd.com/read/29485973/self-adjuvanting-nanoemulsion-targeting-dendritic-cell-receptor-clec9a-enables-antigen-specific-immunotherapy
#8
Bijun Zeng, Anton Pj Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G Baxter, Meghna Talekar, Davide Moi, Kirsteen M Tullett, Irina Caminschi, Mireille H Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction...
May 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29464946/uptake-of-tio-2-nanoparticles-into-c-elegans-neurons-negatively-affects-axonal-growth-and-worm-locomotion-behavior
#9
Chun-Chih Hu, Gong-Her Wu, Tzu-En Hua, Oliver I Wagner, Ta-Jen Yen
We employ model organism Caenorhabditis elegans to effectively study the toxicology of anatase and rutile phase titanium dioxide (TiO2 ) nanoparticles (NPs). The experimental results show that nematode C. elegans can take up fluorescein isothiocyanate-labeled TiO2 NPs and that both anatase and rutile TiO2 NPs can be detected in the cytoplasm of cultured primary neurons imaged by transmission electron microscopy. After TiO2 NP exposure, these neurons also grow shorter axons, which may be related to the detected impeded worm locomotion behavior...
March 14, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29446689/platelets-and-vascular-integrity
#10
Carsten Deppermann
Platelets patrol the vasculature and adhere at sites of vascular damage after trauma to limit blood loss. In recent years, however, it has become clear that platelets also contribute to pathophysiologic processes such as thrombosis, atherosclerosis, stroke, sepsis and many more. An exciting new role for them is in non-classical hemostasis to prevent bleeding in the inflamed vasculature. Recent studies suggest that GPVI, CLEC-2, integrin αIIbβ3 (GPIIb/IIIa), and the content of platelet α- and dense granules are important players in this process...
February 15, 2018: Platelets
https://www.readbyqxmd.com/read/29394131/epitope-mapping-of-monoclonal-antibody-pmab-52-against-cat-podoplanin
#11
Yao-Wen Chang, Mika K Kaneko, Shinji Yamada, Yukinari Kato
The mucin-type membrane glycoprotein podoplanin (PDPN) is frequently overexpressed in numerous malignant cancers, including squamous cell carcinoma, germinal neoplasia, mesothelioma, lung cancer, oral cancer, and brain tumor. PDPN expression is strongly associated with cancer progression and poor prognosis. Furthermore, PDPN binds to C-type lectin-like receptor 2 (CLEC-2) on platelets, followed by PDPN-mediated platelet aggregation to facilitate tumor metastasis. We have previously reported a novel anti-cat PDPN (cPDPN) monoclonal antibody (mAb), PMab-52, which specifically detects cPDPN using flow cytometry analysis and successfully identifies cPDPN in feline squamous cell carcinomas...
February 2, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29347990/establishment-of-an-in-vitro-chicken-epithelial-cell-line-model-to-investigate-eimeria-tenella-gamete-development
#12
Françoise I Bussière, Alisson Niepceron, Alix Sausset, Evelyne Esnault, Anne Silvestre, Robert A Walker, Nicholas C Smith, Pascale Quéré, Fabrice Laurent
BACKGROUND: Eimeria tenella infection leads to acute intestinal disorders responsible for important economic losses in poultry farming worldwide. The life-cycle of E. tenella is monoxenous with the chicken as the exclusive host; infection occurs in caecal epithelial cells. However, in vitro, the complete life-cycle of the parasite has only been propagated successfully in primary chicken kidney cells, which comprise undefined mixed cell populations; no cell line model has been able to consistently support the development of the sexual stages of the parasite...
January 18, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29301754/maintenance-of-murine-platelet-homeostasis-by-the-kinase-csk-and-phosphatase-cd148
#13
Jun Mori, Zoltan Nagy, Giada Di Nunzio, Christopher W Smith, Mitchell J Geer, Rashid Al Ghaithi, Johanna P van Geffen, Silke Heising, Luke Boothman, Bibian M E Tullemans, Joao N Correia, Louise Tee, Marijke J E Kuijpers, Paul Harrison, Johan W M Heemskerk, Gavin E Jarvis, Alexander Tarakhovsky, Arthur Weiss, Alexandra Mazharian, Yotis A Senis
Src family kinases (SFKs) coordinate the initiating and propagating activation signals in platelets, but it remains unclear how they are regulated. Here, we show that ablation of C-terminal Src kinase (Csk) and receptor-like protein tyrosine-phosphatase CD148 in mice results in a dramatic increase in platelet SFK activity, demonstrating that these proteins are essential regulators of platelet reactivity. Paradoxically, Csk/CD148-deficient mice exhibit reduced in vivo and ex vivo thrombus formation and increased bleeding following injury rather than a prothrombotic phenotype...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29296975/cell-surface-c-type-lectin-like-receptor-clec-1-dampens-dendritic-cell-activation-and-downstream-th17-responses
#14
Maria Dolores Lopez Robles, Annaick Pallier, Virginie Huchet, Laetitia Le Texier, Severine Remy, Cecile Braudeau, Laurence Delbos, Aurelie Moreau, Cedric Louvet, Carole Brosseau, Pierre-Joseph Royer, Antoine Magnan, Franck Halary, Regis Josien, Maria-Cristina Cuturi, Ignacio Anegon, Elise Chiffoleau
Dendritic cells (DCs) represent essential antigen-presenting cells that are critical for linking innate and adaptive immunity, and influencing T-cell responses. Among pattern recognition receptors, DCs express C-type lectin receptors triggered by both exogenous and endogenous ligands, therefore dictating pathogen response, and also shaping T-cell immunity. We previously described in rat, the expression of the orphan C-type lectin-like receptor-1 (CLEC-1) by DCs and demonstrated in vitro its inhibitory role in downstream T helper 17 (Th17) activation...
March 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295843/gpvi-signaling-is-compromised-in-newly-formed-platelets-after-acute-thrombocytopenia-in-mice
#15
Shuchi Gupta, Deya Cherpokova, Markus Spindler, Martina Morowski, Markus Bender, Bernhard Nieswandt
At sites of vascular injury, exposed subendothelial collagens trigger platelet activation and thrombus formation by interacting with the immunoreceptor tyrosine-based activation motif (ITAM)-coupled glycoprotein VI (GPVI) on the platelet surface. Platelets are derived from the cytoplasm of megakaryocytes (MKs), which extend large proplatelets into bone marrow (BM) sinusoids that are then released into the bloodstream, where final platelet sizing and maturation occurs. The mechanisms that prevent activation of MKs and forming proplatelets in the collagen-rich BM environment remain largely elusive...
March 8, 2018: Blood
https://www.readbyqxmd.com/read/29208681/hemitam-a-single-tyrosine-motif-that-packs-a-punch
#16
REVIEW
Björn Bauer, Alexander Steinle
Innate immune cells sense danger through a plethora of germline-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs) or cellular molecules that are exposed only by stressed, infected, malignant, or dead cells. Many of these danger-sensing receptors belong to the C-type lectin-like superfamily (CLSF) and therefore are called C-type lectin-like receptors (CTLRs). Certain activating CTLRs, namely, CLEC-2, Dectin-1, DNGR-1, NKp80, and NKp65, which are encoded by genes that are clustered together in a subregion of the mammalian natural killer gene complex (NKC), use a single copy tyrosine signaling module termed the hemi-immunoreceptor tyrosine-based activation motif (hemITAM)...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29187378/platelet-glycoprotein-vi-aids-in-local-immunity-during-pneumonia-derived-sepsis-caused-by-gram-negative-bacteria
#17
Theodora A M Claushuis, Alex F de Vos, Bernard Nieswandt, Louis Boon, Joris J T H Roelofs, Onno J de Boer, Cornelis van 't Veer, Tom van der Poll
Platelet collagen receptor glycoprotein VI (GPVI) and podoplanin receptor C-type lectin-like receptor 2 (CLEC2) are receptors implicated in platelet activation that both signal via an immunoreceptor tyrosine-based activation motif. Platelets are necessary for host defense and prevention of hemorrhage during sepsis, but the role of platelet GPVI and CLEC2 herein is unknown. To investigate this, we infected mice depleted of platelet GPVI or CLEC2 by antibody treatment or GPVI-/- mice with the common human sepsis pathogen Klebsiella pneumoniae via the airways to induce pneumonia-derived sepsis...
February 22, 2018: Blood
https://www.readbyqxmd.com/read/29146820/platelet-clec-2-a-molecule-with-2-faces
#18
COMMENT
Lijun Xia
No abstract text is available yet for this article.
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29146750/trpm7-kinase-controls-calcium-responses-in-arterial-thrombosis-and-stroke-in-mice
#19
Sanjeev K Gotru, Wenchun Chen, Peter Kraft, Isabelle C Becker, Karen Wolf, Simon Stritt, Susanna Zierler, Heike M Hermanns, Deviyani Rao, Anne-Laure Perraud, Carsten Schmitz, René P Zahedi, Peter J Noy, Michael G Tomlinson, Thomas Dandekar, Masayuki Matsushita, Vladimir Chubanov, Thomas Gudermann, Guido Stoll, Bernhard Nieswandt, Attila Braun
OBJECTIVE: TRPM7 (transient receptor potential cation channel, subfamily M, member 7) is a ubiquitously expressed bifunctional protein comprising a transient receptor potential channel segment linked to a cytosolic α-type serine/threonine protein kinase domain. TRPM7 forms a constitutively active Mg2+ and Ca2+ permeable channel, which regulates diverse cellular processes in both healthy and diseased conditions, but the physiological role of TRPM7 kinase remains largely unknown. APPROACH AND RESULTS: Here we show that point mutation in TRPM7 kinase domain deleting the kinase activity in mice ( Trpm7 R/R ) causes a marked signaling defect in platelets...
February 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29090969/expression-of-cat-podoplanin-in-feline-squamous-cell-carcinomas
#20
Shunsuke Itai, Shinji Yamada, Mika K Kaneko, Hiroyuki Harada, Yumiko Kagawa, Satoru Konnai, Yukinari Kato
Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis...
December 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
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