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https://www.readbyqxmd.com/read/29146820/platelet-clec-2-a-molecule-with-2-faces
#1
Lijun Xia
No abstract text is available yet for this article.
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29146750/trpm7-transient-receptor-potential-melastatin-like-7-channel-kinase-controls-calcium-responses-in-arterial-thrombosis-and-stroke-in-mice
#2
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 melastatin-like 7 channel) 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 Mg(2+) and Ca(2+) 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...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29090969/expression-of-cat-podoplanin-in-feline-squamous-cell-carcinomas
#3
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...
November 1, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29090616/mouse-podoplanin-supports-adhesion-and-aggregation-of-platelets-under-arterial-shear-a-novel-mechanism-of-haemostasis
#4
Stephanie E Lombard, Alice Y Pollitt, Craig E Hughes, Ying Di, Tom Mckinnon, Chris A O'callaghan, Steve P Watson
The podoplanin-CLEC-2 axis is critical in mice for prevention of hemorrhage in the cerebral vasculature during mid-gestation. This raises the question as to how platelets are captured by podoplanin on neuroepithelial cells in a high shear environment. In this study, we demonstrate that mouse platelets form stable aggregates on mouse podoplanin at arterial shear through a CLEC-2 and Src kinase-dependent pathway. Adhesion and aggregation are also dependent on the platelet glycoprotein (GP) receptors, integrin αIIbβ3 and GPIb, and the feedback agonists ADP and thromboxane A2 (TxA2)...
November 1, 2017: Platelets
https://www.readbyqxmd.com/read/29052966/targeting-of-c-type-lectin-like-receptor-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides-reply
#5
C Delierneux, N Donis, L Servais, O Wéra, P Lancellotti, C Oury
In a recent issue of the Journal of Thrombosis and Haemostasis, we published a study demonstrating that phosphorothioate (PS)-modified CpG oligodeoxynucleotides (PS-CpG ODN) types A, B, and C activate platelets via CLEC-2 [1]. This study followed an initial article by Flierl et al. showing that PS-CpG ODN type C exerts platelet activating effect through GPVI [2]. In a Letter to the Editor, Flierl et al. now present new computational modeling data confirming that PS-CpG ODN type C can bind to CLEC-2 monomers or homodimers, or even to two homodimers, and would therefore be able to cause receptor clustering on platelet surface...
October 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29052937/targeting-of-c-type-lectin-like-receptor-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides-comment
#6
U Flierl, T L Nero, B Lim, R K Andrews, M W Parker, E E Gardiner, K Peter
We read with great interest the article by Delierneux et al. [1] in the Journal of Thrombosis and Haemostasis. The authors elegantly describe a mechanism of platelet activation by CpG oligodeoxynucleotides (ODNs) through CLEC-2 mediated binding and uptake. This is the second platelet activation mechanism to be attributed to CpG ODNs, the first being the one described by our group involving platelet-specific collagen receptor glycoprotein VI (GPVI) [2]. CpG ODNs are short single-stranded DNA molecules resembling bacterial DNA and they were developed as potential drug candidates, largely due to their immunostimulatory properties via activation of toll-like receptor 9 (TLR9) [3]...
October 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28992650/platelet-clec-2-roles-beyond-hemostasis
#7
Katsue Suzuki-Inoue, Nagaharu Tsukiji, Toshiaki Shirai, Makoto Osada, Osamu Inoue, Yukio Ozaki
No abstract text is available yet for this article.
October 9, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28878118/podoplanin-is-a-negative-regulator-of-th17-inflammation
#8
Alyssa N Nylander, Gerald D Ponath, Pierre-Paul Axisa, Mayyan Mubarak, Mary Tomayko, Vijay K Kuchroo, David Pitt, David A Hafler
Recent data indicate that there are different subpopulations of Th17 cells that can express a regulatory as opposed to an inflammatory gene signature. The transmembrane glycoprotein PDPN is critical in the development of multiple organs including the lymphatic system and has been described on T cells in mouse models of autoimmune Th17 inflammation. Here, we demonstrate that unlike in mice, PDPN+ T cells induced under classic Th17-polarizing conditions express transcription factors associated with Th17 cells but do not produce IL-17...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28839100/platelet-clec-2-protects-against-lung-injury-via-effects-of-its-ligand-podoplanin-on-inflammatory-alveolar-macrophages-in-the-mouse
#9
Sian Lax, Julie Rayes, Surasak Wichaiyo, Elizabeth J Haining, Kate Lowe, Beata Grygielska, Ryan Laloo, Per Flodby, Zea Borok, Edward D Crandall, David Thickett, Steve P Watson
There is no therapeutic intervention proven to prevent the acute respiratory syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes which occur during ARDS, however the mechanisms remain elusive. The platelet receptor C-type lectin-like 2 (CLEC-2) has been shown to regulate vascular integrity at sites of acute inflammation. Therefore, the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS...
August 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28835437/clec-2-contributes-to-hemostasis-independently-of-classical-hemitam-signaling-in-mice
#10
Elizabeth J Haining, Deya Cherpokova, Karen Wolf, Isabelle C Becker, Sarah Beck, Johannes A Eble, David Stegner, Steve P Watson, Bernhard Nieswandt
C-type lectin-like receptor 2 (CLEC 2) is a platelet receptor that is critical during development in blood-lymph separation and implicated in thrombus stability in thrombosis and hemostasis. It is the only known platelet activatory receptor that participates in both these aspects of platelet function and is the only one to signal through a hemi-immunoreceptor tyrosine-based activation motif (hemITAM). Current investigations into the function of CLEC 2 in vivo have focused on knock-out studies in which both the receptor and its signaling are deleted, making it impossible to explore the possible signaling independent functions of the receptor which are indicated by its only known physiological ligand, podoplanin, being an integral membrane protein...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28737447/pmab-52-specific-and-sensitive-monoclonal-antibody-against-cat-podoplanin-for-immunohistochemistry
#11
Shinji Yamada, Shunsuke Itai, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Yao-Wen Chang, Saori Handa, Hiroyuki Harada, Yumiko Kagawa, Osamu Ichii, Satoru Konnai, Mika K Kaneko, Yukinari Kato
Podoplanin (PDPN) is expressed in several normal tissues, such as lymphatic endothelial cells, podocytes of renal glomerulus, and type I alveolar cells of lung. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet. Although monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, rabbit PDPN, dog PDPN, and bovine PDPN have been established, anticat PDPN (cPDPN) mAbs have not been developed. In this study, we immunized mice with Chinese hamster ovary (CHO)-K1 cell lines expressing cPDPN, and developed anti-cPDPN mAbs...
October 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28727496/modulation-of-vegf-induced-migration-and-network-formation-by-lymphatic-endothelial-cells-roles-of-platelets-and-podoplanin
#12
Stacey A Langan, Leyre Navarro-Núñez, Steve P Watson, Gerard B Nash
Lymphatic endothelial cells (LEC) express the transmembrane receptor podoplanin whose only known endogenous ligand CLEC-2 is found on platelets. Both podoplanin and CLEC-2 are required for normal lymphangiogenesis as mice lacking either protein develop a blood-lymphatic mixing phenotype. We investigated the roles of podoplanin and its interaction with platelets in migration and tube formation by LEC. Addition of platelets or antibody-mediated crosslinking of podoplanin inhibited LEC migration induced by vascular endothelial growth factors (VEGF-A or VEGF-C), but did not modify basal migration or the response to basic fibroblast growth factor or epidermal growth factor...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28705934/gq-pathway-regulates-proximal-c-type-lectin-like-receptor-2-clec-2-signaling-in-platelets
#13
COMPARATIVE STUDY
Rachit Badolia, Vaishali Inamdar, Bhanu Kanth Manne, Carol Dangelmaier, Johannes A Eble, Satya P Kunapuli
Platelets play a key role in the physiological hemostasis or pathological process of thrombosis. Rhodocytin, an agonist of the C-type lectin-like receptor-2 (CLEC-2), elicits powerful platelet activation signals in conjunction with Src family kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase γ2 (PLCγ2). Previous reports have shown that rhodocytin-induced platelet aggregation depends on secondary mediators such as thromboxane A2 (TxA2) and ADP, which are agonists for G-protein-coupled receptors (GPCRs) on platelets...
September 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28674748/platelet-activating-factor-podoplanin-from-discovery-to-drug-development
#14
Ai Takemoto, Kenichi Miyata, Naoya Fujita
Tumor cell-induced platelet aggregation facilitates hematogenous metastasis by promoting tumor embolization, preventing immunological assaults and shear stress, and the platelet-releasing growth factors support tumor growth and invasion. Podoplanin, also known as Aggrus, is a type I transmembrane mucin-like glycoprotein and is expressed on wide range of tumor cells. Podoplanin has a role in platelet aggregation and metastasis formation through the binding to its platelet receptor, C-type lectin-like receptor 2 (CLEC-2)...
July 3, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28504613/chlpmab-23-cancer-specific-human-mouse-chimeric-anti-podoplanin-antibody-exhibits-antitumor-activity-via-antibody-dependent-cellular-cytotoxicity
#15
Mika K Kaneko, Takuro Nakamura, Akiko Kunita, Masashi Fukayama, Shinji Abe, Yasuhiko Nishioka, Shinji Yamada, Miyuki Yanaka, Noriko Saidoh, Kanae Yoshida, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Podoplanin is expressed in many cancers, including oral cancers and brain tumors. The interaction between podoplanin and its receptor C-type lectin-like receptor 2 (CLEC-2) has been reported to be involved in cancer metastasis and tumor malignancy. We previously established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-23 (IgG1, kappa), one of the mouse anti-podoplanin mAbs, was shown to be a CasMab. However, we have not shown the usefulness of LpMab-23 for antibody therapy against podoplanin-expressing cancers...
June 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28385772/clec-2-podoplanin-and-thromboinflammation
#16
Katsue Suzuki-Inoue
No abstract text is available yet for this article.
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28332312/antitumor-activity-of-chlpmab-2-a-human-mouse-chimeric-cancer-specific-antihuman-podoplanin-antibody-via-antibody-dependent-cellular-cytotoxicity
#17
Mika K Kaneko, Shinji Yamada, Takuro Nakamura, Shinji Abe, Yasuhiko Nishioka, Akiko Kunita, Masashi Fukayama, Yuki Fujii, Satoshi Ogasawara, Yukinari Kato
Human podoplanin (hPDPN), a platelet aggregation-inducing transmembrane glycoprotein, is expressed in different types of tumors, and it binds to C-type lectin-like receptor 2 (CLEC-2). The overexpression of hPDPN is involved in invasion and metastasis. Anti-hPDPN monoclonal antibodies (mAbs) such as NZ-1 have shown antitumor and antimetastatic activities by binding to the platelet aggregation-stimulating (PLAG) domain of hPDPN. Recently, we developed a novel mouse anti-hPDPN mAb, LpMab-2, using the cancer-specific mAb (CasMab) technology...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor%C3%A2-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#18
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
Essentials CpG oligodeoxynucleotide (ODN) immuotherapeutics cause undesired platelet activating effects. It is crucial to understand the mechanisms of these effects to identify protective strategies. CpG ODN-induced platelet activation depends on C-type lectin-like receptor 2 (CLEC-2) and P2Y12. Targeting CLEC-2 or P2Y12 fully prevents CpG ODN-induced platelet activation and thrombosis. SUMMARY: Background Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (ODNs) show potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment...
May 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28294559/the-platelet-activating-receptor-c-type-lectin-receptor-2-plays-an-essential-role-in-liver-regeneration-after-partial-hepatectomy-in-mice
#19
H Kono, H Fujii, K Suzuki-Inoue, O Inoue, S Furuya, K Hirayama, Y Akazawa, Y Nakata, C Sun, N Tsukiji, T Shirai, Y Ozaki
Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx. SUMMARY: Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice...
May 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28157429/chimeric-anti-human-podoplanin-antibody-nz-12-of-lambda-light-chain-exerts-higher-antibody-dependent-cellular-cytotoxicity-and-complement-dependent-cytotoxicity-compared-with-nz-8-of-kappa-light-chain
#20
Mika K Kaneko, Shinji Abe, Satoshi Ogasawara, Yuki Fujii, Shinji Yamada, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Yasuhiko Nishioka, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG2a, lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis...
February 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
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