Browsing by Subject "Platelet"

Now showing 1 - 7 of 7
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    Collagen-platelet interaction, platelet non-integrin receptors
    (Murcia : F. Hernández, 1999) Chiang, T.M.
    Platelet-collagen interaction is a complex event that involves ligand-receptor interaction. There are many adhesive non-integrin receptors for platelets to interact with various types of collagens. These nonintegrin receptors also serve as signal transducers both from the outside of platelets to the inside and possibly vice versa. The present review covers basic aspects of non-integrin receptor function and various signal transduction pathways.
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    Critical role of von Willebrand factor and platelet interaction in venous thromboembolism
    (Murcia : F. Hernández, 2009) Takahashi, Misaki; Yamashita, Atsushi; Moriguchi-Goto, Sayaka; Marutsuka, Kousuke; Sato, Yuichiro; Yamamoto, Hiroshi; Koshimoto, Chihiro; Asada, Yujiro
    It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation.
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    Dawning of the age of genomics for platelet granule disorders: improving insight, diagnosis and management
    (Wiley, 2016-12-16) Bariana, Tadbir K.; Ouwehand, Willem H.; Guerrero López, José Antonio; Gomez, Keith; Medicina Interna
    Inherited disorders of platelet granules are clinically heterogeneous and their prevalence is underestimated because most patients do not undergo a complete diagnostic work-up. The lack of a genetic diagnosis limits the ability to tailor management, screen family members, aid with family planning, predict clinical progression and detect serious consequences, such as myelofibrosis, lung fibrosis and malignancy, in a timely manner. This is set to change with the introduction of high throughput sequencing (HTS) as a routine clinical diagnostic test. HTS diagnostic tests are now available, affordable and allow parallel screening of DNA samples for variants in all of the 80 known bleeding, thrombotic and platelet genes. Increased genetic diagnosis and curation of variants is, in turn, improving our understanding of the pathobiology and clinical course of inherited platelet disorders. Our understanding of the genetic causes of platelet granule disorders and the regulation of granule biogenesis is a work in progress and has been significantly enhanced by recent genomic discoveries from high-powered genome-wide association studies and genome sequencing projects. In the era of whole genome and epigenome sequencing, new strategies are required to integrate multiple sources of big data in the search for elusive, novel genes underlying granule disorders.
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    Estudio in vitro del efecto de las células madre mesenquimales de líquido amniótico sobre la función plaquetaria
    (Universidad de Murcia, 2018-11-19) Fernández-Arrausi García-Estañ, Marina; Marín Atucha, Noemí; Romecin Duran, Paola Alejandra; Escuela Internacional de Doctorado
    Introducción: Las células madre mesenquimales (CMM) obtenidas a partir de tejidos extraembrionarios, respresentan una nueva fuente de células madre para su uso en terapia celular. Están exentas de los problemas éticos y potencial tumorogénico asociados a las células madre embrionarias. Y respecto a las células madre adultas, presentan una mayor capacidad de proliferación y de diferenciación. Una de las fuentes de las CMM es el líquido amniótico, las cuales han demostrado tener excelentes propiedades inmunomoduladoras, antiinflamatorias, así como baja inmunogenicidad y teratogenicidad en transplantes in vivo. Recientemente, se han descrito efectos secundarios, principalmente fenómenos trombóticos cuando se administran las CMM por vía intravenosa. Estos efectos adversos se han relacionado con una mayor expresión del factor tisular, el cual activaría la vía extrínseca de la coagulación produciendo finalmente trombina. Se ha visto como las CMM interactúan con otras células, entre ellas las plaquetas, elementos con un papel fundamental en la hemostasia. Objetivos: El objetivo prinicpal es evaluar el efecto in vitro de las células madre mesenquimales de líquido amniótico (CMM-LA) sobre la función plaquetaria. Como objetivos secundarios nos planteamos el aislamiento, cultivo, caracterización de CMM-LA obtenidas de partos a término, analizar el efecto de las CMM-LA sobre la agregación y adhesión, evaluar el efecto de las CMM-LA sobre la expresión de marcadores de activación plaquetaria y el estudio del efecto de las CMM-LA sobre los niveles citoplasmáticos del calcio plaquetario. Material y métodos: las CMM se obtuvieron de líquidos amnióticos (LA) de cesáreas programadas de partos a término. Posteriormente se cultivaron en medio Amniomed, realizando un seguimiento del cultivo cada 48-72 horas. A los 30 días, se evaluó su capacidad de diferenciación a condrocitos, adipocitos y osteocitos, así como su identificación realizando la caracterización fenotípica. Así mismo se llevó a cabo el análisis molecular de las CMM-LA. En cuanto al análisis del efecto de las CMM-LA sobre la función plaquetaria se realizaron los ensayos clásicos de PFA-100 y Multiplate. Por citometría de flujo también se analizó el efecto de las CMM-LA sobre la agregación plaquetaria, sobre la expresión de marcadores de activación plaquetaria y sobre los niveles citoplasmáticos del calcio plaquetar. Resultados: Los cultivos de CMM-LA mostraron alta proliferación, capacidad de diferenciación y expresaron los maracadores mesenquimales CD105+, CD90+ y CD73+ y los factores de la coagulación y adhesión: factor VIII, factor de von Willebrand, factor tisular y podoplanina, siendo negativas para los marcadores hematopoyéticos CD45- y CD34-. En cuanto al estudio del efecto de las CMM-LA sobre la función plaquetaria, no se observaron diferencias por el analizador PFA-100. Por el contrario, el sistema Multiplate y el análisis por citometría de flujo sí mostraron cambios en la agregación y activación plaquetaria (expresión de P-selectina) tanto basalmente como en presencia de agonistas. Al evaluar el calcio plaquetario por citometría de flujo, observamos como la presencia de CMM-LA produce un ligero aumento de calcio citoplasmático en las plaquetas aisladas, mantenido solo en presencia de calcio extracelular, por el contrario las plaquetas que si interaccionan con las CMM-LA mostraron un progresivo y significativo aumento del calcio citoplasmático. Al realizar los mismos experimentos con heparina, cuya función es inhibir la producción de trombina, se observaron cambios significativos en la agregación, donde se observó una reducción de la respuesta, en la activación donde se disminuyó aún más la expresión de P-selectina, y en el aumento de calcio citoplasmático plaquetario de los agregados. Conclusiones: El líquido amniótio obtenido de partos a término es una fuente adecuada para la obtención de CMM. Las CMM-LA inducen cambios en la función plaquetaria, independientemente de sus efectos procoagulantes.
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    Modulatory role of IL10 in endothelial cell damage and platelet adhesion
    (Murcia : F. Hernández, 2003) Gimeno, M.J.; Pascual, G.; García-Honduvilla, N.; Prieto, A.; Alvarez de Mon, M.; Bellón, J.M.; Buján, J.
    This study explores the possibility of a regulatory role for cytokine IL-10 in platelet aggregation as an active vascular repair mechanism. Endothelial cells from human umbilical cord vein were cultured in the presence of different IL-10 concentrations (0-100 ng/ml). Platelet-rich plasma was then added to these cultures and allowed to act for 30 minutes. To rule out blood plasma involvement, washed platelets were also incubated with IL-10 (0-100 ng/ml). Changes in endothelial cell morphology were observed depending on the IL-10 concentration used; apoptotic cells appearing at the highest IL-10 concentration. Greatest platelet adhesion was noted at the highest IL-10 concentration. It was concluded that, in this in vitro model, low IL-10 levels do not affect cell viability or the pattern of platelet adhesion, but at high doses, this cytokine induces cell death and enhances platelet deposition.
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    Platelet ad hesion receptors and (patho)physiological thrombus formation
    (Murcia : F. Hernández, 2001) Andrews, R.K.; Shen, Y.; Gardiner, E.E.; Berndt, M.C.
    In thrombus formation associated with hemostasis or thrombotic disease, blood platelets first undergo a rapid transition from a circulating state to an adherent state, followed by activation and aggregation. Under flow conditions in the bloodstream, this process potentially involves platelet-platelet, plateletendothelium, platelet-subendothelial matrix, and platelet-leukocyte interactions. Specific adhesion receptors on platelets mediate these interactions, by engaging counter-receptors on other cells, or noncellular ligands in the plasma or matrix. The glycoprotein (GP) Ib-IX-V complex on platelets initiates adhesion at high shear stress by binding the adhesive ligand, von Willebrand Factor (vWF). GP Ib-IX-V may also mediate platelet-endothelium or platelet-leukocyte adhesion, by recognition of P-selectin or Mac-1, respectively. Other membrane glycoproteins, such as the collagen receptor GP VI, may trigger platelet activation at low shear rates. Engagement of GP Ib-IX-V or GP VI leads ultimately to platelet aggregation mediated by the integrin, aIIbB3 (GP IIb-IIIa). This review will focus on recent advances in understanding structure-activity relationships of GP Ib-IX-V, its role in initiating thrombus formation, and its emerging relationships with other vascular cell adhesion receptors.
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    Research progress on the correlation between platelet aggregation and tumor progression
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Chen, Yuyu; Yuan, Jialong; Tang, Faqing; Liu, Qinglin; Huang, Hongjun; Liu, Huan; Liu, Hao
    Platelets are generally considered as the main functional unit of the coagulation system. However, more and more studies have confirmed that platelets also have an important relationship with tumor progression. Tumor cells can utilize platelets to promote their own infiltration and hematogenous metastasis, and platelets are activated and aggregated in this process. Therefore, platelet aggregation may be a concomitant marker of tumor progression. This is of great significance for predicting tumor metastasis before timely treatments.