Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope

Mrvar-Brečko, Anita; Šuštar, Vid; Janša, Vid; Štukelj, Roman; Janša, Rado; Mujagić, Emir; Kruljc, Peter; Iglič, Aleš; Hägerstrand, Henry; Kralj‐Iglič, Veronika

doi:10.1016/j.bcmd.2010.02.003

Cited by 69 publications

(50 citation statements)

References 30 publications

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“…6,20 Injury-associated microparticles provide a surface that may enable initiation of complement activation, and the small size of microparticles may enable them to enter most body fluids. 31,32 Microparticles are present in normal serum and circulate in continuous contact with complement proteins. Thus, the nature of the microparticles and their abundance in plasma may have a profound influence on complement homeostasis throughout the body.…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Renner¹,

Klawitter²,

Goldberg³

et al. 2013

Journal of the American Society of Nephrology

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Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.

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Section: Discussionmentioning

confidence: 99%

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Renner¹,

Klawitter²,

Goldberg³

et al. 2013

Journal of the American Society of Nephrology

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“…17,18 Information on the presence of tumors could be obtained from cell-derived nanovesicles which are expected to be found in body fluids, such as blood, synovial fluid, ascites, pleural fluid, and cerebrospinal fluid. 19,20 For example, it was recently demonstrated that tumors of various origin 21 and various clinical outcomes 22 can be classified by their micro RNA (miRNA) profiles. miRNAs are short (about 18-25 nucleotides long) noncoding RNAs, including small interfering RNA, ribosomal RNA, transfer RNA, and small nuclear RNA.…”

Section: Introductionmentioning

confidence: 99%

Stability of membranous nanostructures: a possible key mechanism in cancer progression

Kralj‐Iglič¹

2012

IJN

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Abstract:Membranous nanostructures, such as nanovesicles and nanotubules, are an important pool of biological membranes. Recent results indicate that they constitute cell-cell communication systems and that cancer development is influenced by these systems. Nanovesicles that are pinched off from cancer cells can move within the circulation and interact with distant cells. It has been suggested and indicated by experimental evidence that nanovesicles can induce metastases from the primary tumor in this way. Therefore, it is of importance to understand better the mechanisms of membrane budding and vesiculation. Here, a theoretical description is presented concerning consistently related lateral membrane composition, orientational ordering of membrane constituents, and a stable shape of nanovesicles and nanotubules. It is shown that the character of stable nanostructures reflects the composition of the membrane and the intrinsic shape of its constituents. An extension of the fluid mosaic model of biological membranes is suggested by taking into account curvature-mediated orientational ordering of the membrane constituents on strongly anisotropically curved regions. Based on experimental data for artificial membranes, a possible antimetastatic effect of plasma constituents via mediation of attractive interaction between membranous structures is suggested. This mediated attractive interaction hypothetically suppresses nanovesiculation by causing adhesion of buds to the mother membrane and preventing them from being pinched off from the membrane.

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“…Vesiculation was studied in cancer cells [9][10][11][12][13] and was shown in vivo to be connected to the impact of cancer-associated coagulopathies. [14][15][16][17] Furthermore, nanoparticles have also been found in isolates from other body fluids, such as synovial fluid of inflamed joints, 18 pleural fluid, 19 ascites, 19 saliva, 20,21 and urine.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles isolated from blood: a reflection of vesiculability of blood cells during the isolation process

Šuštar¹,

Bedina-Zavec²,

Stukelj³

et al. 2011

IJN

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Background: Shedding of nanoparticles from the cell membrane is a common process in all cells. These nanoparticles are present in body fluids and can be harvested by isolation. To collect circulating nanoparticles from blood, a standard procedure consisting of repeated centrifugation and washing is applied to the blood samples. Nanoparticles can also be shed from blood cells during the isolation process, so it is unclear whether nanoparticles found in the isolated material are present in blood at sampling or if are they created from the blood cells during the isolation process. We addressed this question by determination of the morphology and identity of nanoparticles harvested from blood. Methods: The isolates were visualized by scanning electron microscopy, analyzed by flow cytometry, and nanoparticle shapes were determined theoretically. Results: The average size of nanoparticles was about 300 nm, and numerous residual blood cells were found in the isolates. The shapes of nanoparticles corresponded to the theoretical shapes obtained by minimization of the membrane free energy, indicating that these nanoparticles can be identified as vesicles. The concentration and size of nanoparticles in blood isolates was sensitive to the temperature during isolation. We demonstrated that at lower temperatures, the nanoparticle concentration was higher, while the nanoparticles were on average smaller. Conclusion:These results indicate that a large pool of nanoparticles is produced after blood sampling. The shapes of deformed blood cells found in the isolates indicate how fragmentation of blood cells may take place. The results show that the contents of isolates reflect the properties of blood cells and their interaction with the surrounding solution (rather than representing only nanoparticles present in blood at sampling) which differ in different diseases and may therefore present a relevant clinical parameter.

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Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope

Cited by 69 publications

References 30 publications

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

Stability of membranous nanostructures: a possible key mechanism in cancer progression

Nanoparticles isolated from blood: a reflection of vesiculability of blood cells during the isolation process

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