scholarly journals Overview of Platelet Physiology: Its Hemostatic and Nonhemostatic Role in Disease Pathogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Kakali Ghoshal ◽  
Maitree Bhattacharyya
Keyword(s):  
Clinical Research ◽  
Dense Granule ◽  
Renal Diseases ◽  
Vascular Integrity ◽  
Surface Receptors ◽  
Fundamental Biological Process ◽  
Anucleate Cell ◽  
Noninvasive Biomarkers ◽  
Cell Fragments ◽  
Distinct Morphology

Platelets are small anucleate cell fragments that circulate in blood playing crucial role in managing vascular integrity and regulating hemostasis. Platelets are also involved in the fundamental biological process of chronic inflammation associated with disease pathology. Platelet indices like mean platelets volume (MPV), platelets distributed width (PDW), and platelet crit (PCT) are useful as cheap noninvasive biomarkers for assessing the diseased states. Dynamic platelets bear distinct morphology, whereαand dense granule are actively involved in secretion of molecules like GPIIb , IIIa, fibrinogen, vWf, catecholamines, serotonin, calcium, ATP, ADP, and so forth, which are involved in aggregation. Differential expressions of surface receptors like CD36, CD41, CD61 and so forth have also been quantitated in several diseases. Platelet clinical research faces challenges due to the vulnerable nature of platelet structure functions and lack of accurate assay techniques. But recent advancement in flow cytometry inputs huge progress in the field of platelets study. Platelets activation and dysfunction have been implicated in diabetes, renal diseases, tumorigenesis, Alzheimer’s, and CVD. In conclusion, this paper elucidates that platelets are not that innocent as they keep showing and thus numerous novel platelet biomarkers are upcoming very soon in the field of clinical research which can be important for predicting and diagnosing disease state.

Localization of egg cytoplasm that promotes differentiation to epidermis in embryos of the ascidian Halocynthia roretzi

Development ◽  
1994 ◽  
Vol 120 (2) ◽  
pp. 235-243 ◽  
Author(s):  
H. Nishida
Keyword(s):  
Specific Antigen ◽  
Equatorial Region ◽  
Epidermal Cells ◽  
Second Phase ◽  
Halocynthia Roretzi ◽  
Cytoplasmic Factors ◽  
Early Embryos ◽  
Ooplasmic Segregation ◽  
Anucleate Cell ◽  
Cell Fragments

Embryogenesis in ascidians is of the mosaic type. This property suggests the presence of cytoplasmic factors in the egg that are responsible for specification of the developmental fates of early blastomeres. The epidermal cells that surround the entire tadpole larva originate exclusively from blastomeres of the animal hemisphere of early embryos. To obtain direct evidence for cytoplasmic determinants of epidermis fate, we carried out cytoplasmic transfer experiments by fusing blastomeres and anucleate cell fragments from various regions of eggs and embryos. Initially, presumptive non-epidermis blastomeres (blastomeres from the vegetal hemisphere) were fused to cytoplasmic fragments from various regions of blastomeres of 8-cell embryos of Halocynthia roretzi, and development of epidermal cells was monitored by following the expression of an epidermis- specific antigen, as well as by observations of morphology and the secretion of larval tunic materials. Formation of epidermis was observed when vegetal blastomeres were fused with cytoplasmic fragments from the presumptive epidermis blastomeres. The results suggested that cytoplasmic factors that promoted epidermis differentiation (epidermis determinants) were present in epidermis progenitors. Vegetal blastomeres only manifested this change in fate when fused with cytoplasmic fragments of roughly equal or larger size. Next, to examine the presence and localization of epidermis determinants in the uncleaved egg, cytoplasmic fragments from various regions of unfertilized and fertilized eggs were fused with the vegetal blastomeres. The results suggested that epidermis determinants were already present in unfertilized eggs and that they were segregated by movements of the ooplasm after fertilization. After the first phase of ooplasmic segregation, these determinants were widely distributed, with the highest activity being located in the equatorial region. There were no indications of regional differences in the activity within the equatorial region of eggs at this stage. After the second phase of ooplasmic segregation, prior to the first cleavage, the activity moved in the animal direction, namely, to the animal hemisphere, from which future epidermis-lineage blastomeres are normally formed.

scholarly journals Heterotrimeric Gα12/13 proteins in kidney injury and disease

2020 ◽  
Vol 318 (3) ◽  
pp. F660-F672
Author(s):  
Elena Tutunea-Fatan ◽  
Jasper C. Lee ◽  
Bradley M. Denker ◽  
Lakshman Gunaratnam
Keyword(s):  
Kidney Injury ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Interaction Networks ◽  
Renal Diseases ◽  
Accessory Proteins ◽  
Guanine Nucleotide ◽  
Guanine Nucleotide Binding Protein ◽  
Surface Receptors ◽  
Guanine Nucleotide Binding

Gα12 and Gα13 are ubiquitous members of the heterotrimeric guanine nucleotide-binding protein (G protein) family that play central and integrative roles in the regulation of signal transduction cascades within various cell types in the kidney. Gα12/Gα13 proteins enable the kidney to adapt to an ever-changing environment by transducing stimuli from cell surface receptors and accessory proteins to effector systems. Therefore, perturbations in Gα12/Gα13 levels or their activity can contribute to the pathogenesis of various renal diseases, including renal cancer. This review will highlight and discuss the complex and expanding roles of Gα12/Gα13 proteins on distinct renal pathologies, with emphasis on more recently reported findings. Deciphering how the different Gα12/Gα13 interaction networks participate in the onset and development of renal diseases may lead to the discovery of new therapeutic strategies.

scholarly journals Hemostasis vs. homeostasis: Platelets are essential for preserving vascular barrier function in the absence of injury or inflammation

2020 ◽  
Vol 117 (39) ◽  
pp. 24316-24325 ◽  
Author(s):  
Shuchi Gupta ◽  
Christoph Konradt ◽  
Adam Corken ◽  
Jerry Ware ◽  
Bernhard Nieswandt ◽  
...  
Keyword(s):  
Barrier Function ◽  
Dense Granule ◽  
Severe Thrombocytopenia ◽  
Barrier Dysfunction ◽  
Vascular Integrity ◽  
Lectin Receptor ◽  
Dense Granules ◽  
Dense Granule Secretion ◽  
Granule Secretion ◽  
Time Required

Platelets are best known for their vasoprotective responses to injury and inflammation. Here, we have asked whether they also support vascular integrity when neither injury nor inflammation is present. Changes in vascular barrier function in dermal and meningeal vessels were measured in real time in mouse models using the differential extravasation of fluorescent tracers as a biomarker. Severe thrombocytopenia produced by two distinct methods caused increased extravasation of 40-kDa dextran from capillaries and postcapillary venules but had no effect on extravasation of 70-kDa dextran or albumin. This reduction in barrier function required more than 4 h to emerge after thrombocytopenia was established, reverting to normal as the platelet count recovered. Barrier dysfunction was also observed in mice that lacked platelet-dense granules, dense granule secretion machinery, glycoprotein (GP) VI, or the GPVI signaling effector phospholipase C (PLC) γ2. It did not occur in mice lacking α-granules, C type lectin receptor-2 (CLEC-2), or protease activated receptor 4 (PAR4). Notably, although both meningeal and dermal vessels were affected, intracerebral vessels, which are known for their tighter junctions between endothelial cells, were not. Collectively, these observations 1) highlight a role for platelets in maintaining vascular homeostasis in the absence of injury or inflammation, 2) provide a sensitive biomarker for detecting changes in platelet-dependent barrier function, 3) identify which platelet processes are required, and 4) suggest that the absence of competent platelets causes changes in the vessel wall itself, accounting for the time required for dysfunction to emerge.

scholarly journals Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?

Cancers ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 133 ◽  
Author(s):  
Marion Lavergne ◽  
Emily Janus-Bell ◽  
Mathieu Schaff ◽  
Christian Gachet ◽  
Pierre Mangin
Keyword(s):  
Tumor Metastasis ◽  
Platelet Adhesion ◽  
Cell Interaction ◽  
Main Role ◽  
Experimental Metastasis ◽  
Pharmacological Agents ◽  
Surface Receptors ◽  
Wall Injury ◽  
Cell Fragments

Platelets are small anucleated cell fragments that ensure the arrest of bleeding after a vessel wall injury. They are also involved in non-hemostatic function such as development, immunity, inflammation, and in the hematogeneous phase of metastasis. While the role of platelets in tumor metastasis has been recognized for 60 years, the molecular mechanism underlying this process remains largely unclear. Platelets physically and functionally interact with various tumor cells through surface receptors including integrins. Platelets express five integrins at their surface, namely α2β1, α5β1, α6β1, αvβ3, and αIIbβ3, which bind preferentially to collagen, fibronectin, laminin, vitronectin, and fibrinogen, respectively. The main role of platelet integrins is to ensure platelet adhesion and aggregation at sites of vascular injury. Two of these, α6β1 and αIIbβ3, were proposed to participate in platelet–tumor cell interaction and in tumor metastasis. It has also been reported that pharmacological agents targeting both integrins efficiently reduce experimental metastasis, suggesting that platelet integrins may represent new anti-metastatic targets. This review focuses on the role of platelet integrins in tumor metastasis and discusses whether these receptors may represent new potential targets for novel anti-metastatic approaches.

scholarly journals Start a fire, kill the bug: The role of platelets in inflammation and infection

2018 ◽  
Vol 24 (6) ◽  
pp. 335-348 ◽  
Author(s):  
Carsten Deppermann ◽  
Paul Kubes
Keyword(s):  
Immune Cells ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Oxygen Species ◽  
Vascular Integrity ◽  
Surface Receptors ◽  
Extracellular Traps

Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation. In this review we summarize the current knowledge about how platelets interact with the innate immune system during inflammation and infection and highlight recent advances in the field.

Erythrophagocytosis in the Liver in Hemolytic Anemias

1968 ◽  
Vol 26 ◽  
pp. 184-185
Author(s):  
O. T. Minick ◽  
E. Orfei ◽  
F. Volini ◽  
G. Kent
Keyword(s):  
Acid Phosphatase ◽  
Oxidative Damage ◽  
Phosphatase Activity ◽  
Kupffer Cells ◽  
Acid Phosphatase Activity ◽  
Common Type ◽  
Red Cell ◽  
Cell Fragments ◽  
Reticulo Endothelial System ◽  
Important Site

Hemolytic anemias were produced in rats by administering phenylhydrazine or anti-erythrocytic (rooster) serum, the latter having agglutinin and hemolysin titers exceeding 1:1000.Following administration of phenylhydrazine, the erythrocytes undergo oxidative damage and are removed from the circulation by the cells of the reticulo-endothelial system, predominantly by the spleen. With increasing dosage or if animals are splenectomized, the Kupffer cells become an important site of sequestration and are greatly hypertrophied. Whole red cells are the most common type engulfed; they are broken down in digestive vacuoles, as shown by the presence of acid phosphatase activity (Fig. 1). Heinz body material and membranes persist longer than native hemoglobin. With larger doses of phenylhydrazine, erythrocytes undergo intravascular fragmentation, and the particles phagocytized are now mainly red cell fragments of varying sizes (Fig. 2).

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

A rapid silver-impregnation technique on ultra-thin sections for Electron Microscopy

1993 ◽  
Vol 51 ◽  
pp. 242-243
Author(s):  
K. Chien ◽  
R.C. Heusser ◽  
M.L. Jones ◽  
R.L. Van de Velde
Keyword(s):  
Electron Microscopy ◽  
Silver Nitrate ◽  
Silver Impregnation ◽  
Sodium Borate ◽  
Renal Diseases ◽  
Distilled Water ◽  
Thin Sections ◽  
Impregnation Technique ◽  
Centrifuge Tube ◽  
Simplified Procedure

Silver impregnation techniques have been used for the demonstration of the complex carbohydrates in electron microscopy. However, the silver stains were believed to be technically sensitive and time consumming to perform. Currently, due to the need to more specifically evaluate immune complex for localization in certain renal diseases, a simplified procedure in conjunction with the use of the microwave has been developed and applied to renal and other biopsies. The procedure is as follows:Preparation of silver methenamine solution:1. 15ml graduated, clear polystyrene centrifuge tube (Falcon, No. 2099) was rinsed once with distilled water.2. 3% hexamethylene tetramine (methenamine) was added into the centrifuge tube to the 6ml mark.3. 3% silver nitrate was added slowly to the methenamine to the 7ml mark while agitating. (Solution will instantly turn milky in color and then clear rapidly by mixing. No precipitate should be formed).4. 2% sodium borate was added to the solution to the 8ml mark, mixed and centrifuged before use.

Ultra high resolution SEM at high voltage images individual fab fragments applied as molecular label to cell surface receptors

1989 ◽  
Vol 47 ◽  
pp. 70-71
Author(s):  
Klaus-Ruediger Peters
Keyword(s):  
High Resolution ◽  
High Energy ◽  
Metal Coating ◽  
Beam Diameter ◽  
Surface Receptors ◽  
Surface Mobility ◽  
Metal Atoms ◽  
Shadowing Effect ◽  
Imaging Mode ◽  
Deposition Techniques

Topographic ultra high resolution can now routinely be established on bulk samples in cold field emission scanning electron microscopy with a second generation of microscopes (FSEM) designed to provide 0.5 nm probe diameters. If such small probes are used for high magnification imaging, topographic contrast is so high that remarkably fine details can be imaged on 2DMSO/osmium-impregnated specimens at ribosome surfaces even without a metal coating. On TCH/osmium-impregnated specimens topographic resolution can be increased further if the SE-I imaging mode is applied. This requires that beam diameter and metal coating thickness be made smaller than the SE range of ~1 nm and background signal contributions be reduced. Subnanometer small probes can be obtained (only) at high accelerating voltages. Subnanometer thin continuous metal films can be produced under the following conditions: self-shadowing effect between metal atoms must be reduced through appropriate deposition techniques and surface mobility of metal atoms must be diminished through high energy sputtering and/or specimen cooling.

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