Procoagulant tissue factor-exposing vesicles in human seminal fluid

Franz, Claudia; Böing, Anita N.; Hau, Chi M.; Montag, Markus; Strowitzki, T.; Nieuwland, Rienk; Tóth, Bettina

doi:10.1016/j.jri.2013.02.002

Cited by 19 publications

(18 citation statements)

References 26 publications

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“…7C right panel ). When an antibody against the aminopeptidase expressed on prostasomes (CD13) was used [ 79 , 80 ], no decrease of CD13 + prostasomes was observed ( Fig. 7C left panel ), suggesting that prostasomes are not cleared by these sPLA 2 s. Thus, we demonstrate that sPLA 2 V and X efficiently hydrolyze the PS on MPs present in the seminal fluid.…”

Section: Resultsmentioning

confidence: 78%

Detection and Quantification of Microparticles from Different Cellular Lineages Using Flow Cytometry. Evaluation of the Impact of Secreted Phospholipase A2 on Microparticle Assessment

et al. 2015

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Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification. Here, flow cytometry with improved methodology for microparticle resolution was used to detect microparticles of human and mouse species generated from platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells from the male reproductive tract. A family of soluble proteins, the secreted phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with microparticles in biological fluids and that catalyze the hydrolysis of membrane phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid frequently used to assess microparticles, and might even clear microparticles, we further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and X, on microparticle quantification. We observed that if enriched in fluids, certain sPLA2 enzymes impair the quantification of microparticles depending on the species studied, the source of microparticles and the means of detection employed (surface phosphatidylserine or protein antigen detection). This study provides analytical considerations for appropriate interpretation of microparticle cytofluorometric measurements in biological samples containing sPLA2 enzymes.

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Section: Resultsmentioning

confidence: 78%

Detection and Quantification of Microparticles from Different Cellular Lineages Using Flow Cytometry. Evaluation of the Impact of Secreted Phospholipase A2 on Microparticle Assessment

et al. 2015

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“…However, platelet α granules have a structure similar to that of multivesicular endosomes and demonstrate intraluminal nanovesicular structures that have been termed exosomes (45). Terms related to complement and coagulation are also increasingly recognized as features of extracellular vesicles and are again not entirely unexpected from the analysis (46, 47). However, a cluster of gene ontology terms suggesting protease inhibitor activity (Fig.…”

Section: Resultsmentioning

confidence: 82%

Proteomics Analysis of Cancer Exosomes Using a Novel Modified Aptamer-based Array (SOMAscanTM) Platform

Webber

Stone

Katilius

et al. 2014

Molecular & Cellular Proteomics

139

114

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We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (slow off-rate modified aptamers) and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were highly purified from the Du145 prostate cancer cell line, by pooling selected fractions from a continuous sucrose gradient (within the density range of 1.1 to 1.2 g/ml), and examined under standard conditions or with additional detergent treatment by the SOMAscanTM array (version 3.0). Lysates of Du145 cells were also prepared, and the profiles were compared. Housekeeping proteins such as cyclophilin-A, LDH, and Hsp70 were present in exosomes, and we identified almost 100 proteins that were enriched in exosomes relative to cells. These included proteins of known association with cancer exosomes such as MFG-E8, integrins, and MET, and also those less widely reported as exosomally associated, such as ROR1 and ITIH4. Several proteins with no previously known exosomal association were confirmed as exosomally expressed in experiments using individual SOMAmer® reagents or antibodies in micro-plate assays. Western blotting confirmed the SOMAscanTM-identified enrichment of exosomal NOTCH-3, L1CAM, RAC1, and ADAM9. In conclusion, we describe here over 300 proteins of hitherto unknown association with prostate cancer exosomes and suggest that the SOMAmer®-based assay technology is an effective proteomics platform for exosome-associated biomarker discovery in diverse clinical settings.

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“…In contrast, body fluids exposed to the "milieu extérieur" such as seminal fluid, 25 synovial fluid, 26 urine, 18 and saliva 18 of healthy human subjects all contain high levels of coagulant TFMP. A likely reason for the presence of TFMP in these fluids is that they provide a permanent, additional source of extravascular TF to facilitate hemostasis upon injury, thereby minimizing blood loss and reducing the risk of infection.…”

Section: Tf-exposing Mp In Healthy and Diseased Individualsmentioning

confidence: 99%

Clinical Significance of Tissue Factor–Exposing Microparticles in Arterial and Venous Thrombosis

Bleker

Sturk

et al. 2015

Semin Thromb Hemost

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Microparticles (MP) are small extracellular vesicles (30-1,000 nm) that are released from activated cells or platelets. Exposure of negatively charged phospholipids and tissue factor (TF) renders MP procoagulant. Normal plasma levels of intravascular TF-exposing MP (TFMP) are low, but their number may rise in pathological conditions, including cancer and infectious disease. Emerging evidence indicates an important role for these circulating TFMP in the pathogenesis of thrombotic complications such as venous thromboembolism and disseminated intravascular coagulation, whereas their contribution to arterial thrombosis is less studied. Despite serious limitations of the currently available assays for measuring TFMP levels or the procoagulant activity associated with TFMP with respect to sensitivity and specificity, the scientific interest in TFMP is rapidly growing because their application as prognostic biomarkers for thrombotic complications is promising. Future advances in detection methods will likely provide more insight into TFMP and eventually improve their clinical utility.

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Procoagulant tissue factor-exposing vesicles in human seminal fluid

Cited by 19 publications

References 26 publications

Detection and Quantification of Microparticles from Different Cellular Lineages Using Flow Cytometry. Evaluation of the Impact of Secreted Phospholipase A2 on Microparticle Assessment

Detection and Quantification of Microparticles from Different Cellular Lineages Using Flow Cytometry. Evaluation of the Impact of Secreted Phospholipase A2 on Microparticle Assessment

Proteomics Analysis of Cancer Exosomes Using a Novel Modified Aptamer-based Array (SOMAscanTM) Platform

Clinical Significance of Tissue Factor–Exposing Microparticles in Arterial and Venous Thrombosis

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