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Platelet integrin

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https://www.readbyqxmd.com/read/29227167/diagnosis-of-platelet-function-disorders-a-standardized-rational-and-modular-flow-cytometric-approach
#1
Oliver Andres, Katja Henning, Gabriele Strauß, Annerose Pflug, Georgi Manukjan, Harald Schulze
A high proportion of patients with mucocutaneous bleeding diathesis and suspected inherited or acquired platelet disorder remain without diagnosis even after comprehensive laboratory testing. Since flow cytometry allows investigation of resting and activated platelets on the single cell level by requiring only minimal amounts of blood, this method has become an important assay within the diagnostic algorithm, especially in pediatrics. We therefore developed a standardized and modular flow cytometric approach that contributes to clarify impaired platelet function in a rational step-by-step manner...
December 11, 2017: Platelets
https://www.readbyqxmd.com/read/29215030/traf3-negatively-regulates-platelet-activation-and-thrombosis
#2
Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li
CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211557/acoustophoretic-purification-of-platelets-feasibility-and-impact-on-platelet-activation-and-function
#3
Pierre Bohec, Jérémie Gachelin, Véronique Ollivier, Thibaut Mutin, Xavier Télot, Benoît Ho-Tin-Noé, Sandra Sanfilippo
Purity, limited platelet activation, and preservation of platelet function are important stakes of preparation of platelet concentrates (PC) for clinical use. In fact, contaminating red blood cells and leukocytes, as well as activated and/or poorly functional platelets in PC, represents a risk of poor efficiency and adverse side effects during platelet transfusion. Therefore, optimization of preparation and storage of PC is still an active field of research. Shear-induced platelet activation is an unwanted side effect of the hard-spin (up to 5000g) step of centrifugation-based methods currently used in blood banks to prepare PC from whole blood samples...
December 6, 2017: Platelets
https://www.readbyqxmd.com/read/29197873/comparative-anti-platelet-profiling-reveals-a-potent-anti-aggregatory-effect-of-cd34-progenitor-cell-derived-late-outgrowth-endothelial-cells-in-vitro
#4
Vasileios G Chantzichristos, Fani Gkrozou, Konstantinos Stellos, Minas E Paschopoulos, Alexandros D Tselepis
BACKGROUND/AIMS: Platelets affect endothelial progenitor cell (EPC) functionality, inducing their differentiation into mature endothelial cells. However, it remains to be established whether EPCs can influence platelet functionality. METHODS: Mononuclear proangiogenic cells (MPCs) and early outgrowth cells (EOCs) were prepared from peripheral blood mononuclear cells, whereas late-outgrowth endothelial cells (OECs) were prepared from cord blood CD34+ cells. The effect of the above cells and their supernatants on washed platelet aggregation was studied...
December 2, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/29195072/platelets-on-your-marks-get-set-migrate
#5
Sarah K Bambach, Tim Lämmermann
The idea that anucleate platelets display autonomous migration has long been viewed with skepticism. Gaertner et al. provide in vivo evidence that platelets undergo active migration at sites of thrombus formation and in inflamed liver sinusoids. Integrin-dependent migration allows platelets to scavenge and bundle fibrin-bound material, including intravascular bacteria.
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29178985/a-complementary-role-for-tetraspanin-superfamily-member-tssc6-and-adp-purinergic-p2y12-receptor-in-platelets
#6
Mohammed Makkawi, David Howells, Mark D Wright, Denise E Jackson
Tumor-suppressing subchromosomal transferable fragment cDNA 6 (TSSC6) expression is restricted to hematopoietic organs and tissues where it plays a role in hematopoietic-cell function. The ADP purinergic receptor P2Y12 is mainly expressed by platelets with important clinical significance as a target for several clinically approved antithrombotic agents. We have previously shown a physical association between P2Y12 and TSSC6 in platelets. Hence our aim was to investigate whether this physical association is translated to functional effects...
November 15, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29157825/1-6-di-o-caffeoyl-%C3%AE-d-glucopyranoside-a-natural-compound-from-callicarpa-nudiflora-hook-impairs-p2y12-and-thromboxane-a2-receptor-mediated-amplification-of-platelet-activation-and-aggregation
#7
Jianjiang Fu, Xiaocui Zhu, Wei Wang, Hong Lu, Zhoumiao Zhang, Ting Liu, Huanjun Xu, Huizheng Fu, Shuangcheng Ma, Yuehua Luo
BACKGROUND: Platelet activation and subsequent accumulation at sites of vascular injury perform a central role in thrombus formation, which is believed to be the trigger of several cardiovascular diseases, such as atherosclerosis, myocardial infarction and strokes. In this sense, the search for agents that are capable of blocking platelets aggregation has important implications for these diseases. Callicarpa nudiflora (C. nudiflora) Hook is a traditional Chinese medicine herb for eliminating stasis to subdue swelling and hemostasis...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29118993/cellular-characteristics-of-keratin-19-positive-canine-hepatocellular-tumours-explain-its-aggressive-behaviour
#8
Renee G van Sprundel, Ted Sgam van den Ingh, Baukje A Schotanus, Monique E van Wolferen, Louis C Penning, Jan Rothuizen, Bart Spee
The expression of the hepatic progenitor cell marker keratin 19 (K19) in canine hepatocellular carcinomas is linked with a poor prognosis. To better understand this aggressive behaviour, K19-positive hepatocellular carcinomas (n=5) and K19-negative hepatocellular adenomas (n=6) were immunohistochemically stained for proteins involved in malignant tumour development. The K19-positive carcinomas showed marked positivity for platelet-derived growth factor receptor alpha polypeptide (PDGFRα), laminin, integrin beta-1/CD29, B-cell-specific Moloney murine leukaemia virus Integration site 1, glypican-3 (GPC-3) and prominin-1/CD133, in contrast with K19-negative hepatocellular adenomas...
2017: Veterinary Record Open
https://www.readbyqxmd.com/read/29104956/deletion-of-the-arp2-3-complex-in-megakaryocytes-leads-to-microthrombocytopenia-in-mice
#9
David S Paul, Caterina Casari, Congying Wu, Raymond Piatt, Swetha Pasala, Robert A Campbell, Kathryn O Poe, Dorsaf Ghalloussi, Robert H Lee, Jeremy D Rotty, Brian C Cooley, Kellie R Machlus, Joseph E Italiano, Andrew S Weyrich, James E Bear, Wolfgang Bergmeier
Actin reorganization regulates key processes in platelet activation. Here we examined the role of the Arp2/3 complex, an essential component in actin filament branching, in platelet function. The Arpc2 gene, encoding the p34 subunit of the Arp2/3 complex, was deleted in the megakaryocyte lineage (Arpc2(fl/fl)PF4-Cre). Deletion of the Arp2/3 complex resulted in marked microthrombocytopenia in mice, caused by premature platelet release into the bone marrow compartment and impaired platelet survival in circulation...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29101791/calpain-1-regulates-platelet-function-in-a-humanized-mouse-model-of-sickle-cell-disease
#10
Jennifer O Nwankwo, Thomas Gremmel, Anja J Gerrits, Farha J Mithila, Rod R Warburton, Nicholas S Hill, Yunzhe Lu, Lauren J Richey, Joseph A Jakubowski, Andrew L Frelinger, Athar H Chishti
One of the major contributors to sickle cell disease (SCD) pathobiology is the hemolysis of sickle red blood cells (RBCs), which release free hemoglobin and platelet agonists including adenosine 5'-diphosphate (ADP) into the plasma. While platelet activation/aggregation may promote tissue ischemia and pulmonary hypertension in SCD, modulation of sickle platelet dysfunction remains poorly understood. Calpain-1, a ubiquitous calcium-activated cysteine protease expressed in the hematopoietic cells, mediates aggregation of platelets in healthy mice...
October 26, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29097692/quantitative-structural-mechanobiology-of-platelet-driven-blood-clot-contraction
#11
Oleg V Kim, Rustem I Litvinov, Mark S Alber, John W Weisel
Blood clot contraction plays an important role in prevention of bleeding and in thrombotic disorders. Here, we unveil and quantify the structural mechanisms of clot contraction at the level of single platelets. A key elementary step of contraction is sequential extension-retraction of platelet filopodia attached to fibrin fibers. In contrast to other cell-matrix systems in which cells migrate along fibers, the "hand-over-hand" longitudinal pulling causes shortening and bending of platelet-attached fibers, resulting in formation of fiber kinks...
November 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/29090616/mouse-podoplanin-supports-adhesion-and-aggregation-of-platelets-under-arterial-shear-a-novel-mechanism-of-haemostasis
#12
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/29090484/mutations-of-the-integrin-%C3%AE-iib-%C3%AE-3-intracytoplasmic-salt-bridge-cause-macrothrombocytopenia-and-enlarged-platelet-%C3%AE-granules
#13
Marie Favier, Jean-Claude Bordet, Remi Favier, Vasiliki Gkalea, Xavier Pillois, Philippe Rameau, Najet Debili, Marie-Christine Alessi, Paquita Nurden, Hana Raslova, Alan Nurden
Rare gain-of-function mutations within the ITGA2B or ITGB3 genes have been recognized to cause macrothrombocytopenia (MTP). Here we report three new families with autosomal dominant (AD) MTP, two harboring the same mutation of ITGA2B, αIIbR995W, and a third family with an ITGB3 mutation, β3D723H. In silico analysis shows how the two mutated amino acids directly modify the salt bridge linking the intra-cytoplasmic part of αIIb to β3 of the integrin αIIbβ3. For all affected patients, the bleeding syndrome and MTP was mild to moderate...
November 1, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29080903/human-endoglin-as-a-potential-new-partner-involved-in-platelet-endothelium-interactions
#14
Elisa Rossi, Miguel Pericacho, Christilla Bachelot-Loza, Dominique Pidard, Pascale Gaussem, Sonia Poirault-Chassac, Francisco J Blanco, Carmen Langa, Consuelo González-Manchón, Jose M Lopez Novoa, David M Smadja, Carmelo Bernabeu
Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. This vascular disease is characterized by a bleeding tendency that is postulated to be a consequence of telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition...
October 28, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29073606/inhibitory-effect-of-afatinib-on-platelet-activation-and-apoptosis
#15
Hang Cao, Abdulla Al Mamun Bhuyan, Anja T Umbach, Rosi Bissinger, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is used for the treatment of several malignancies. Afatinib is at least partially effective by triggering apoptosis of tumor cells. Platelets may similarly undergo apoptosis, which is characterized by caspase 3 activation, cell shrinkage and phosphatidylserine translocation. However, an effect of afatinib on platelets has never been reported. The present study explored whether treatment of platelets with afatinib modifies platelet activation and apoptosis in the absence and presence of platelet activators thrombin or collagen related peptide (CRP)...
October 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29061963/%C3%AE-v-integrins-on-mesenchymal-cells-regulate-skeletal-and-cardiac-muscle-fibrosis
#16
I R Murray, Z N Gonzalez, J Baily, R Dobie, R J Wallace, A C Mackinnon, J R Smith, S N Greenhalgh, A I Thompson, K P Conroy, D W Griggs, P G Ruminski, G A Gray, M Singh, M A Campbell, T J Kendall, J Dai, Y Li, J P Iredale, H Simpson, J Huard, B Péault, N C Henderson
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ(+) cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ(+) cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29052936/a-humanized-monoclonal-antibody-that-inhibits-platelet-surface-erp72-reveals-a-role-for-erp72-in-thrombosis
#17
L Holbrook, G K Sandhar, P Sasikumar, M P Schenk, A R Stainer, K Sahli, G D Flora, A B Bicknell, J M Gibbins
BACKGROUND: Within the endoplasmic reticulum, thiol isomerase enzymes modulate the formation and rearrangement of disulphide bonds in newly folded proteins entering the secretory pathway to ensure correct protein folding. In addition to their intracellular importance, thiol isomerases have been recently identified to be present on the surface of a number of cell types where they are important for cell function. Several thiol isomerases are known to be present on the resting platelet surface including PDI, ERp5 and ERp57 and levels are increased following platelet activation...
October 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29045015/the-small-molecule-mertk-inhibitor-unc2025-decreases-platelet-activation-and-prevents-thrombosis
#18
Brian R Branchford, Timothy J Stalker, Luke Law, Gilbert Acevedo, Susan Sather, Christine Brzezinski, Katina M Wilson, Katherine Minson, Alisa B Lee-Sherick, Pavel Davizon-Castillo, Christopher Ng, Weihe Zhang, Keith B Neeves, Steven R Lentz, Xiaodong Wang, Stephen V Frye, H Shelton Earp, Deborah DeRyckere, Lawrence F Brass, Douglas K Graham, Jorge A Di Paola
BACKGROUND: Gas6 signals through the TAM (TYRO-3, AXL, MERTK) receptor family mediating platelet activation and thrombus formation via activation of the aggregate-stabilizing αIIb β3 integrin. OBJECTIVE: Here we describe anti-thrombotic effects mediated by UNC2025, a small molecule MERTK tyrosine kinase inhibitor. METHODS: MERTK phosphorylation and downstream signaling were assessed by immunoblot. Light transmission aggregometry, flow cytometry, and microfluidic analysis were used to evaluate the impact of MERTK inhibition on platelet activation and stability of aggregate formation in vitro...
October 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29038247/constitutive-activation-of-integrin-%C3%AE-9-augments-self-directed-hyperplastic-and-proinflammatory-properties-of-fibroblast-like-synoviocytes-of-rheumatoid-arthritis
#19
Takashi Emori, Jun Hirose, Kotoko Ise, Jun-Ichiro Yomoda, Michiko Kasahara, Tadanobu Shinkuma, Hiroyuki Yoshitomi, Hiromu Ito, Motomu Hashimoto, Shingo Sugahara, Hirotada Fujita, Nobuchika Yamamoto, Yoshiaki Morita, Shuh Narumiya, Ichiro Aramori
Despite advances in the treatment of rheumatoid arthritis (RA), currently approved medications can have significant side effects due to their direct immunosuppressive activities. Additionally, current therapies do not address residual synovial inflammation. In this study, we evaluated the role of integrin α9 and its ligand, tenascin-C (Tn-C), on the proliferative and inflammatory response of fibroblast-like synoviocytes (FLSs) from RA patients grown in three-dimensional (3D)-micromass culture. FLSs from osteoarthritis patients, when grown in the 3D-culture system, formed self-directed lining-like structures, whereas FLSs from RA tissues (RA-FLSs) developed an abnormal structure of condensed cellular accumulation reflective of the pathogenic features of RA synovial tissues...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29034237/proteomics-of-eosinophil-activation
#20
REVIEW
Deane F Mosher, Emily M Wilkerson, Keren B Turton, Alexander S Hebert, Joshua J Coon
We recently identified and quantified >7,000 proteins in non-activated human peripheral blood eosinophils using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and described phosphoproteomic changes that accompany acute activation of eosinophils by interleukin-5 (IL5) (1). These data comprise a treasure trove of information about eosinophils. We illustrate the power of label-free LC-MS/MS quantification by considering four examples: complexity of eosinophil STATs, contribution of immunoproteasome subunits to eosinophil proteasomes, complement of integrin subunits, and contribution of platelet proteins originating from platelet-eosinophil complexes to the overall proteome...
2017: Frontiers in Medicine
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