Search

Objective: Circulating cell-derived microparticles have been reported to be elevated in inflammatory and procoagulant conditions including deep infiltrating endometriosis. The objective of this pilot study was to investigate whether higher circulating cell-derived microparticle levels may be associated with specific clinical features and the extension or severity of deep infiltrating endometriosis. Methods: This is an observational analytical cross-sectional study, including three groups of patients undergoing gynecological surgery. The DIE group included 75 patients with deep infiltrating endometriosis, the control group (C group) consisted of 39 patients without endometriosis, and a positive control group was composed of 31 patients with ovarian endometriomas but not deep infiltrating endometriosis (OE group). Venous blood samples for circulating cell-derived microparticle determinations in plasma were obtained before surgery. The following variables were assessed: severe dysmenorrhea, dyspareunia, non-cyclic chronic pelvic pain, dyschezia, dysuria, hematuria, rectal bleeding, sterility, presence of ovarian endometrioma, adenomyosis, and adhesions, rASRM (revised American Society for Reproductive Medicine) stage, Enzian classification, number of sites affected, and the cumulative size of deep infiltrating endometrial implants. Results: Circulating cell-derived microparticle levels were statistically higher in the DIE group compared with the C group ( p-value = 0.001). None of the variables analyzed showed higher levels of circulating cell-derived microparticles in the DIE group, except for a significant positive correlation between the cumulative size of deep infiltrating endometrial lesions and circulating cell-derived microparticle levels ( r = 0.264, p = 0.022). Conclusion: Patients having deep infiltrating endometriosis with a larger cumulative size of endometriotic implants showed higher circulating cell-derived microparticle levels suggesting an increased inflammatory and/or hypercoagulable systemic status in this more severe form of the disease. Further research is needed to assess our findings and to explore the role of circulating cell-derived microparticles in the pathophysiology of deep infiltrating endometriosis.

Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 &micro, m size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.

Cardiovascular diseases (CVDs) are a common cause of death, and a search for biomarkers for risk stratification is warranted. Elevated levels of cell-derived microparticles (MPs) are found in patients with CVD and in groups with risk factors for CVD. Subpopulations of MPs are promising biomarkers for improving risk prediction, as well as monitoring treatment. However, the field has been hampered by technical difficulties, and the ongoing development of sensitive standardized techniques is crucial for implementing MP analyses in the clinic. Large prospective studies are required to establish which MPs are of prognostic value in different patient groups. In this review, we discuss methodological challenges and progress in the field, as well as MP populations that are of interest for further clinical evaluation.

Introduction: Circulating cell-derived microparticles (MPs) have been implicated in several disease processes and elevated levels are found in many pathological conditions. The detection and accurate measurement of MPs, although attracting widespread interest, is hampered by a lack of standardisation. The aim of this study was to establish a reliable flow cytometric assay to measure distinct subtypes of MPs in disease and to identify any significant causes of variability in MP quantification. Materials and Methods: Circulating MPs within plasma were identified by their phenotype (platelet, endothelial, leukocyte and annexin-V positivity (AnnV+). The influence of key variables (i.e. time between venepuncture and centrifugation, washing steps, the number of centrifugation steps, freezing/long-term storage and temperature of thawing) on MP measurement were investigated. Results: Increasing time between venepuncture and centrifugation leads to increased MP levels. Washing samples results in decreased AnnV+ MPs (P = 0.002) and platelet-derived MPs (PMPs) (P = 0.002). Double centrifugation of MPs prior to freezing decreases numbers of AnnV+ MPs (P = 0.0004) and PMPs (P = 0.0004). A single freeze thaw cycle of samples led to an increase in AnnV+ MPs (P = 0.0020) and PMPs (P= 0.0039). Long-term storage of MP samples at -80 degrees resulted in decreased MP levels. Conclusions: This study found that minor protocol changes significantly affected MP levels. This is one of the first studies attempting to standardise a method for obtaining and measuring circulating MPs. Standardisation will be essential for successful development of MP technologies, allowing direct comparison of results between studies and leading to a greater understanding of MPs in disease. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved

Background: Circulating microparticle (cMP) levels are increased in the acute phase of ST-elevation myocardial infarction (STEMI) and associate with microvascular obstruction; however, the precise cMP-parental cell signature and activation level are not elucidated. Here, we aimed to study the cMP signature in STEMI-patients and whether cMP phenotype changes in relation to onset of pain-to-PCI [ischemic time (IT)]-elapsed time. Methods: Blood was taken at PCI from the culprit coronary and the peripheral circulation in STEMI-patients (N = 40). Two control groups were included: peripheral blood of age-matched patients recovering from STEMI [after 72 h] and of control individuals (N - 20/group). cMP-parental origin and activation level were characterized by triple-labeling flow cytometry. Results: Procoagulant annexin V-positive cMPs bearing parental cell markers as well as markers of activated cells displayed a significantly different profile in STEMI-patients, in control individuals and in patients recovering from STEMI. cMPs derived from monocytes, endothelium, and activated vascular cells were higher in the culprit coronary artery than in peripheral blood in STEMI-patients, especially in patients intervened at short IT. Indeed, cMP levels in coronary blood were inversely related to IT duration (more abundant in thrombi with pain-toPCI time

Analysis of circulating cell-derived microparticles (MP) is becoming more refined and clinically useful. This review, stemming from lectures given at Tokyo late 2003, does not repeat prior reviews but focuses on new horizons. A major theme is the rising recognition of platelets and their MP (PMP) as key mediators of inflammation/immunity. Among the major concepts developed are that (i) many so-called soluble markers of inflammation are in reality MP-bound; (ii) PMP and other MP appear to serve important signaling and immune functions including antigen presentation. In conclusion, MP analysis is poised to enter the mainstream of clinical testing, measuring specific antigens rather than gross levels. However, more research is needed to decisively establish their functions, and international standards are needed to allow comparing results from different laboratories.

Cell-derived microparticles (MPs), which are biogenic nanosized membrane vesicles that convey bioactive molecules between cells, have exhibited great potential to serve as therapeutic platforms. However, so far, all the MPs used as theranostic vectors in previous studies have been produced in vitro from cell culture supernatants, which is still associated with several concerns regarding practical applications. In this study, circulating MPs (CMPs), which are freshly purified from the peripheral blood of oral squamous cell carcinoma (OSCC) patients, are directly and efficiently embedded with ultrasmall near-infrared-fluorescent magnetic quantum dots (Ag2Se@Mn QDs) via electroporation. By virtue of the superior photostability, favorable biocompatibility, and dual-mode traceability of Ag2Se@Mn QD-labeled CMPs in vivo, the tissue distribution and natural tumor-targeting behavior of CMPs from OSCC patients are directly visualized in living mice for the first time. Moreover, by simultaneously embedding antitumor siRNA and Ag2Se@Mn QDs into CMPs derived from OSCC patients, a dual-modally traceable and actively tumor-targeted nanoplatform for cancer theranostics is developed. This study reports the first reliable conjugation-free labeling strategy for in vivo dual-mode tracking of CMPs harvested from the human body, and, more importantly, reports the development of traceable tumor-targeted theranostic vectors based on naturally occurring CMPs from cancer patients.

International audience; Strenuous exercise is associated with an inflammatory response involving the activation of several types of blood cells. In order to document the specific activation of these cell types, we studied the effect of three maximal exercise tests conducted to exhaustion on the quantitative and qualitative pattern of circulating cell-derived microparticles and inflammatory molecules in healthy subjects. This study mainly indicated that the plasma concentration of microparticles from platelets and polymorphonuclear neutrophils (PMN) was increased immediately after the strenuous exercise. In addition, the increase in plasma concentration of microparticles from PMN and platelets was still observed after 2 hours of recovery. A similar pattern was observed for the IL-6 plasma level. In contrast, no change was observed for either soluble selectins or plasma concentration of microparticles from red blood cells, monocytes and endothelial cells. In agreement, sVCAM-1 and sICAM-1 levels were not changed by the exercise. We conclude that a strenuous exercise is accompanied by platelet-and PMN-derived microparticle production that probably reflects the activation of these two cell types.

Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.

It is now recognized that all circulating blood cells, as well as endothelial cells (EC), continuously shed small membranous vesicles (microparticles [MPs]), which are approximately less than 1 µm, and that levels of circulating MPs are sensitive indicators of disease activity. The first type extensively studied in patients was platelet MP (PMPs) (1). Currently, endothelial-derived MP (EMPs) have risen to the fore as sensitive markers of EC perturbation, recently reviewed (2) and further considered in this article. Although other reviews may differ in viewpoint and emphasis (3,4), it is generally agreed that circulating MPs comprise different subspecies of membrane vesicles released from endothelium and blood cells, such as platelets, leukocytes, and red blood cells (RBCs). MPs containing negatively charged phospatidylserine (PS) and/or tissue factor are highly procoagulant. MPs that express specific adhesion molecules are capable of interacting with leukocytes and endothelia to initiate inflammatory responses.