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Lactadherin

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https://www.readbyqxmd.com/read/30100715/identification-of-novel-target-genes-in-human-lung-tissue-involved-in-chronic-obstructive-pulmonary-disease
#1
Lena Heinbockel, Sebastian Marwitz, Andra B Schromm, Henrik Watz, Christian Kugler, Ole Ammerpohl, Karoline Schnepf, Klaus F Rabe, Daniel Droemann, Torsten Goldmann
Introduction: As part of a study aimed at illuminating at least some of the complex molecular events taking place in COPD, we screened tissues by means of transcriptome analyses. Materials and methods: Tissues were subjected to transcriptome analysis. Candidate genes were identified and validated by immunohistochemistry. Primary human lung cells were subjected to stimulation with cigarette smoke extract for further validation by real time PCR. Results: Six candidate genes were selected for further investigations: Aquaporin 3 ( AQP3 ), extracellular matrix protein 1 ( ECM1 ), four and a half LIM domain 1 ( FHL1 ), milk fat globule epidermal growth factor 8 ( MFGE8 , lactadherin), phosphodiesterase 4D-interacting protein ( PDE4DIP ), and creatine transporter SLC6A8 ...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/30057675/the-exposure-of-phosphatidylserine-influences-procoagulant-activity-in-retinal-vein-occlusion-by-microparticles-blood-cells-and-endothelium
#2
Ying Su, Xueqing Deng, Ruishuang Ma, Zengxiang Dong, Feng Wang, Jialan Shi
The pathogenesis of hypercoagulability in retinal vein occlusion (RVO) is largely unknown. Whether the exposure of phosphatidylserine (PS) and microparticle (MPs) release will affect procoagulant activity (PCA) in RVO needs to be investigated. Objectives . To evaluate PS expression, circulating MPs, and the corresponding PCA in RVO patients. Twenty-five RVO patients were compared with 25 controls. PS-positive cells were detected by flow cytometry. Cell-specific MPs were measured by lactadherin for PS and relevant CD antibody...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/30017878/extracellular-vesicles-containing-il-4-modulate-neuroinflammation-in-a-mouse-model-of-multiple-sclerosis
#3
Giacomo Casella, Federico Colombo, Annamaria Finardi, Hélène Descamps, Gerard Ill-Raga, Antonello Spinelli, Paola Podini, Mattia Bastoni, Gianvito Martino, Luca Muzio, Roberto Furlan
Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery...
September 5, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29941674/von-willebrand-factor-enhances-microvesicle-induced-vascular-leakage-and-coagulopathy-in-mice-with-traumatic-brain-injury
#4
Yingang Wu, Wei Liu, Yuan Zhou, Tristan Hilton, Zilong Zhao, Wei Liu, Min Wang, Jason Yeon, Katie Houck, Perumal Thiagarajan, Fangyi Zhang, Fu-Dong Shi, Xiaoping Wu, Min Li, Jing-Fei Dong, Jianning Zhang
von Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound...
September 6, 2018: Blood
https://www.readbyqxmd.com/read/29879884/disorder-in-milk-proteins-lactadherin-multifunctionality-and-structure
#5
Bassam H Sabha, Fuad Alzahrani, Hussein A Almehdar, Vladimir N Uversky, Elrashdy M Redwan
Milk fat globule membrane (MFGM) is one of the milk components that is produced by the lactating mammary glands and released to the milk in the form of vesicles. MFGM surrounds milk fat globule secreted by the milk producing cells and has a complex structure containing various lipids (e.g., triacylglycerides, phospholipids, and cholesterol), proteins and other macromolecules. Among the proteinaceous components of MFGM is lactadherin, also known as milk fat globule-EGF factor 8 protein (MFG-E8). Being one of the main proteins present in MFGM, lactadherin is related to milk secretion, has antimicrobial and antiviral effects, and plays important roles in the immune defense as one of the immune system molecules...
2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29679947/tissue-factor-coagulant-activity-is-regulated-by-the-plasma-membrane-microenvironment
#6
Yuanjie Yu, Anita N Böing, Chi M Hau, Najat Hajji, Wolfram Ruf, Auguste Sturk, Rienk Nieuwland
BACKGROUND:  Tissue factor (TF) can be present in a non-coagulant and coagulant form. Whether the coagulant activity is affected by the plasma membrane microenvironment is unexplored. OBJECTIVE:  This article studies the presence and coagulant activity of human TF in plasma membrane micro-domains. METHODS:  Plasma membranes were isolated from human MIA PaCa2 cells, MDA-MB-231 cells and human vascular smooth muscle cells by Percoll gradient ultracentrifugation after cell disruption...
June 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29554700/procoagulant-effects-of-low-level-platelet-activation-and-its-inhibition-by-colchicine
#7
Caroline J Reddel, Gabrielle J Pennings, Jennifer L Curnow, Vivien M Chen, Leonard Kritharides
Platelets play an important role in diseases such as cardiovascular disease and cancer, especially through their release of extracellular vesicles (EVs) and role in thrombosis. The effects of the anti-inflammatory drug colchicine on platelets are not well understood. We investigated the effect of colchicine on the release of pro-coagulant EVs from platelets under low-level activation. Citrated platelet-rich plasma (PRP) from healthy donors was incubated with 2 mM colchicine or vehicle at 37°C for 30 minutes with gentle rotation...
April 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29554658/procoagulant-activity-of-blood-and-endothelial-cells-via-phosphatidylserine-exposure-and-microparticle-delivery-in-patients-with-diabetic-retinopathy
#8
Ying Su, Jingli Chen, Zengxiang Dong, Yan Zhang, Ruishuang Ma, Junjie Kou, Feng Wang, Jialan Shi
BACKGROUND/AIMS: The mechanisms for thrombosis in diabetic retinopathy (DR) are complex and need to be further elucidated. The purpose of this study was to test phosphatidylserine (PS) exposure on microparticles (MPs) and MP-origin cells from the circulation and to analyze cell-/MP-associated procoagulant activity (PCA) in DR patients. METHODS: PS-positive MPs and cells from healthy controls (n = 20) and diabetic patients (n = 60) were analyzed by flow cytometry and confocal microscopy...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29547014/meal-intake-increases-circulating-procoagulant-microparticles-in-patients-with-type-1-and-type-2-diabetes-mellitus
#9
Galia Spectre, Fariborz Mobarrez, Ragnhild Stålesen, Claes-Göran Östenson, David Varon, Håkan Wallen, Paul Hjemdahl
Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry...
March 16, 2018: Platelets
https://www.readbyqxmd.com/read/29544920/phosphatidylserine-exposing-blood-cells-and-microparticles-induce-procoagulant-activity-in-non-valvular-atrial-fibrillation
#10
Lixiu Wang, Yayan Bi, Muxin Yu, Tao Li, Dongxia Tong, Xiaoyan Yang, Cong Zhang, Li Guo, Chunxu Wang, Yan Kou, Zengxiang Dong, Valerie A Novakovic, Ye Tian, Junjie Kou, Masood A Shammas, Jialan Shi
BACKGROUND: The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). METHODS: NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy...
May 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29535850/scalable-cgmp-compatible-purification-of-extracellular-vesicles-carrying-bioactive-human-heterodimeric-il-15-lactadherin-complexes
#11
Dionysios C Watson, Bryant C Yung, Cristina Bergamaschi, Bhabadeb Chowdhury, Jenifer Bear, Dimitris Stellas, Aizea Morales-Kastresana, Jennifer C Jones, Barbara K Felber, Xiaoyuan Chen, George N Pavlakis
The development of extracellular vesicles (EV) for therapeutic applications is contingent upon the establishment of reproducible, scalable, and high-throughput methods for the production and purification of clinical grade EV. Methods including ultracentrifugation (U/C), ultrafiltration, immunoprecipitation, and size-exclusion chromatography (SEC) have been employed to isolate EV, each facing limitations such as efficiency, particle purity, lengthy processing time, and/or sample volume. We developed a cGMP-compatible method for the scalable production, concentration, and isolation of EV through a strategy involving bioreactor culture, tangential flow filtration (TFF), and preparative SEC...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29529237/phosphatidylserine-on-microparticles-and-associated-cells-contributes-to-the-hypercoagulable-state-in-diabetic-kidney-disease
#12
Muxin Yu, Rujuan Xie, Yan Zhang, Hui Liang, Li Hou, Chengyuan Yu, Jinming Zhang, Zengxiang Dong, Ye Tian, Yayan Bi, Junjie Kou, Valerie A Novakovic, Jialan Shi
Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30)...
February 26, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29501282/simplified-preparation-of-%C3%AE-v-%C3%AE-3-integrin-targeted-microbubbles-based-on-a-clinically-available-ultrasound-contrast-agent-validation-in-a-tumor-bearing-mouse-model
#13
Kentaro Otani, Hirohito Nishimura, Atsunori Kamiya, Mariko Harada-Shiba
The usefulness of ultrasound molecular imaging with αv β3 integrin-targeted microbubbles for detecting tumor angiogenesis has been demonstrated. Recently, we developed αv β3 integrin-targeted microbubbles by modifying clinically available microbubbles (Sonazoid, Daiichi-Sankyo Pharmaceuticals, Tokyo, Japan) with a secreted glycoprotein (lactadherin). The aims of our present study were to simplify the preparation of lactadherin-bearing Sonazoid and to examine the diagnostic utility of lactadherin-bearing Sonazoid for αv β3 integrin-expressing tumor vessels by using SK-OV-3-tumor-bearing mice...
May 2018: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/29453194/comparison-of-generic-fluorescent-markers-for-detection-of-extracellular-vesicles-by-flow-cytometry
#14
Leonie de Rond, Edwin van der Pol, Chi M Hau, Zoltan Varga, Auguste Sturk, Ton G van Leeuwen, Rienk Nieuwland, Frank A W Coumans
BACKGROUND: Extracellular vesicles (EVs) in biofluids are potential biomarkers of disease. To explore the clinical relevance of EVs, a specific generic EV marker would be useful, one that does not require antibodies and binds to all EVs. Here we evaluated 5 commonly used generic markers for flow cytometry. METHODS: Flow cytometry (A60-Micro, Apogee) was used to evaluate the ability of the generic EV markers calcein acetoxymethyl ester, calcein acetoxymethyl ester violet, carboxyfluorescein succinimidyl ester (CFSE), 4-(2-[6-(dioctylamino)-2-naphthalenyl]ethenyl)-1-(3-sulfopropyl)pyridinium (di-8-ANEPPS), and lactadherin to stain EVs from MCF7 human breast adenocarcinoma cell line-conditioned culture medium [epithelial cell adhesion molecule positive (EpCAM+ )] or platelet EVs from human plasma [integrin β3 positive (CD61+ )]...
April 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29450143/purified-horse-milk-exosomes-contain-an-unpredictable-small-number-of-major-proteins
#15
Sergey E Sedykh, Lada V Purvinish, Artem S Monogarov, Evgeniya E Burkova, Alina E Grigor'eva, Dmitrii V Bulgakov, Pavel S Dmitrenok, Valentin V Vlassov, Elena I Ryabchikova, Georgy A Nevinsky
Exosomes are 40-100 nm nanovesicles containing RNA and different proteins. Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in intracellular communication and immune function. Exosomes from different sources are usually obtained by combination of centrifugation and ultracentrifugation and according to published data can contain from a few dozens to thousands of different proteins. Crude exosome preparations from milk of eighteen horses were obtained for the first time using several standard centrifugations...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29426977/investigation-of-the-phosphatidylserine-binding-properties-of-the-lipid-biosensor-lactadherin-c2-lactc2-in-different-membrane-environments
#16
Kathryn Del Vecchio, Robert V Stahelin
Lipid biosensors are robust tools used in both in vitro and in vivo applications of lipid imaging and lipid detection. Lactadherin C2 (LactC2) was described in 2000 as being a potent and specific sensor for phosphatidylserine (PS) (Andersen et al. Biochemistry 39:6200-6206, 2000). PS is an anionic phospholipid enriched in the inner leaflet of the plasma membrane and has paramount roles in apoptosis, cells signaling, and autophagy. The myriad roles PS plays in membrane dynamics make monitoring PS levels and function an important endeavor...
February 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29334397/recombinant-phosphatidylserine-binding-nanobodies-for-targeting-of-extracellular-vesicles-to-tumor-cells-a-plug-and-play-approach
#17
Sander A A Kooijmans, Jerney J J M Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2)...
February 1, 2018: Nanoscale
https://www.readbyqxmd.com/read/29332224/phosphatidylserine-exposing-blood-and-endothelial-cells-contribute-to-the-hypercoagulable-state-in-essential-thrombocythemia-patients
#18
Dongxia Tong, Muxin Yu, Li Guo, Tao Li, Jihe Li, Valerie A Novakovic, Zengxiang Dong, Ye Tian, Junjie Kou, Yayan Bi, Jinghua Wang, Jin Zhou, Jialan Shi
The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex and not well defined. Our objective was to explore whether phosphatidylserine (PS) exposure on blood cells and endothelial cells (ECs) can account for the increased thrombosis and distinct thrombotic risks among mutational subtypes in ET. Using flow cytometry and confocal microscopy, we found that the levels of PS-exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all P < 0...
April 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29284036/effect-of-innate-antiviral-glycoproteins-in-breast-milk-on-seroconversion-to-rotavirus-vaccine-rotarix-in-children-in-lusaka-zambia
#19
Katayi Mwila-Kazimbaya, Miguel Pugliese Garcia, Samuel Bosomprah, Natasha Makabilo Laban, Caroline Cleopatra Chisenga, Sallie Robey Permar, Michelo Simuyandi, Sody Munsaka, Roma Chilengi
INTRODUCTION: Rotavirus vaccines have been introduced into national immunization programmes to mitigate morbidity and mortality associated rotavirus diarrhoea. Lower vaccine effectiveness has however been noted in low-middle income countries, but little is known about the role of maternal components found in breast milk. This study assessed the effect of lactoferrin, lactadherin, and tenascin-c on rotavirus vaccine seroconversion. METHODS: This was a retrospective cohort study of 128 infants who had been fully immunized with Rotarix™...
2017: PloS One
https://www.readbyqxmd.com/read/29169950/lactadherin-an-unappreciated-haemostasis-regulator-and-potential-therapeutic-agent
#20
REVIEW
Agnieszka Kamińska, Francisco J Enguita, Ewa Ł Stępień
Lactadherin is a small (53-66kDa) multifunctional glycoprotein belonging to the secreted extracellular matrix protein family. It has a multi-domain structure and is involved in many biological and physiological processes, including phagocytosis, angiogenesis, atherosclerosis, tissue remodeling, and haemostasis regulation. Lactadherin binds phosphatidylserine (PS)-enriched cell surfaces in a receptor-independent manner. Interaction between lactadherin and PS is crucial for regulation of blood coagulation processes...
February 2018: Vascular Pharmacology
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