HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (63) Citing Articles via Google Scholar Google Scholar Articles by Hugel, B. Articles by Freyssinet, J.-M. Search for Related Content PubMed PubMed Citation Articles by Hugel, B. Articles by Freyssinet, J.-M.

REVIEW

Membrane Microparticles: Two Sides of the Coin

Bénédicte Hugel, M. Carmen Martínez, Corinne Kunzelmann and Jean-Marie Freyssinet

Institut d’Hématologie et d’Immunologie, Université Louis Pasteur, Faculté de Médecine, Strasbourg, France, and Unité 143 INSERM, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France

jean-marie.freyssinet{at}hemato-ulp.u-strasbg.fr

	Abstract

 
Microparticles are plasma membrane-derived vesicles shed from stimulated cells, in the broad sense of the term. Their presence is interpreted by proximal or remote cells in fundamental physiological processes including intercellular communication, hemostasis, and immunity. On the other hand, variations of their number or characteristics are frequently observed in pathophysiological situations.

	Introduction

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 
In multicellular organisms, homeostasis results from a subtle balance between cell proliferation and degenerescence. Cells differentiate, expand, fulfill particular functions, then undergo programmed death and are finally cleared by phagocytosis. At each stage of its life, the cell is subjected to a variety of stimulations leading to the release of submicron fragments from the plasma membrane, usually termed microparticles or microvesicles (MPs). MPs hijack membrane constituents and cytoplasmic content and survive the cell (FIGURE 1). Owing to the plasticity of the lateral organization of the plasma membrane into raft domains, known to segregate particular proteins and lipid species, a given stimulus can be expected to elicit a "private" response resulting in an inclusive or exclusive sorting. This explains how MPs of the same cellular origin may have different protein and lipid compositions. Hence, such fragments are interpreted in intercellular communication and participate in the maintenance of homeostasis under physiological conditions, or they can initiate a deleterious process in case of excess or when carrying pathogenic constituents. MPs can therefore be considered a disseminated storage pool of bioactive effectors, the nature and proportion of the latter accounting for duality, more particularly evidenced in vascular disease, inflammation, and immunity.

View larger version (62K): [in this window] [in a new window]   FIGURE 1. Cellular microparticles: a disseminated storage pool of bioactive effectors Membrane microparticles are shed from the plasma membrane of stimulated cells. They harbor membrane and carry cytoplasmic proteins as well as bioactive lipids implicated in a variety of fundamental processes. This representation does not intend to be exhaustive with respect to the different hijacked components. MHC, major histocompatibility complex; GPI, glycosylphosphatidylinositol.

	Mechanisms Governing the Plasma Membrane Remodeling

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

View larger version (77K): [in this window] [in a new window]   FIGURE 2. The plasma membrane response to cell stimulation The plasma membrane is a well-structured entity characterized by a controlled transverse distribution of lipids and proteins between the two leaflets but also by a lateral organization in domains termed "rafts." Following stimulation, a general redistribution occurs, leading to raft structuration, phosphatidylserine externalization, and microparticle release. The private membrane response characterized by controlled inclusion or exclusion of specific constituents into rafts leads to the release of microparticles of a particular composition.

A specialized category of MPs with known functions in protein sorting and in the immune response are the exosomes. More homogenous in size and composition, exosome characteristics in different cell types indicate the following minimal requirements for discrimination with MPs: a diameter of 30–90 nm; a density in sucrose gradients of 1.13–1.19 g/ml; an endocytic origin (exosomes do not derive from the plasma membrane but from internal membranes); and enrichment in tetraspaning molecules (48). PS is also present at the surface of exosomes that are derived from platelets and dendritic cells but at (much) lower levels. The aim of this review is not to describe exosomes, which has been done by other authors (48). Briefly, they have a clearing function because of enrichment in some proteins known to decrease or disappear from the cell surface during maturation. Perhaps more importantly, they are also known to harbor major histocompatibility complex molecules, making them responsible for the stimulation of T cells in an antigen-specific manner, promoting an antitumor immune response in vivo. Interestingly, exosomes were recently shown to bear the pathogenic form of the prion protein PrP^Sc (16), as previously described for the normal cellular form, PrP^c, in MPs (21).

	Membrane Microparticles in Intercellular Communication

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 
Antigen transfer and intercellular cross-talk
Several studies point to MP-induced cell stimulation. Leukocyte MPs activate endothelial cells or transfer leukocyte antigens to epithelial cells. This passive acquisition of leukocytic phenotypes is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties (37, 47). Platelet-derived MPs modulate monocyte-endothelial cell interactions and stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells, and they enhance engraftment of hematopoietic progenitor cells (6). MPs bearing Fas ligand can also be shed from the cell surface in a bioactive configuration providing a mechanism for long-range signal-directed apoptosis (3).

MPs may also be used to address morphogens into a developing tissue. These particular MPs, derived from the basolateral membrane of cells, have been termed "argosomes" (23). We have recently observed that MPs generated from apoptotic T cells harbor morphogens of the Hedgehog family and are able to induce differentiation of pluripotent hematopoietic cells toward megakaryocytic lineage (unpublished observations).

These studies demonstrate that MPs can be efficient vectors of biological information from one cell type to another within proximal or remote tissues.

Microparticles and vascular function
Under pathological situations associated with vascular damage such as myocardial infarction or preeclampsia, MPs isolated from the plasma of patients were found to cause damage in isolated arteries (11, 50).

We recently observed that MPs from apoptotic T cells induce endothelial dysfunction in both conductance and resistance arteries by alteration of nitric oxide (NO) and prostacyclin pathways. In addition, circulating MPs from diabetic patients induced endothelial dysfunction and decreased NO synthase expression (36). These data provide a rationale to explain the paracrine role of MPs as vectors of bioactive effectors promoting vascular dysfunction through transcellular exchanges during inflammatory disease. Endothelial NO dysfunction was not observed in all of the studies (11), but they all share the conclusion that MPs impair endothelial function (12, 43). Discrepancies might originate from quantitative and qualitative differences in MPs, stemming from different tissues challenged by different stimuli.

Together, these studies contribute to a better understanding of the deleterious effects of enhanced circulating levels of MPs observed in cardiovascular or immune disorders. Very recently, it has been proposed that MPs from endothelial cells impair endothelial function by altering the redox balance (12).

Microparticles in angiogenesis
MPs shed from tumor cells stimulate metastasis by promoting in vivo neovascularization. Sphingo-myelin seems to be the active component responsible for this proangiogenic potential by stimulating endothelial cell migration, invasion, and tube formation. Some matrix metallo-proteinases present in endothelium-derived MPs and platelet MPs were shown to be potent angiogenic stimulators in vitro (for a recent review, see Ref. 19).

Tissue factor (TF), the major initiator of blood coagulation, serves as a regulator of angiogenesis, tumor growth, and metastasis (34). TF mediates upregulation of the proangiogenic vascular endothelial growth factor, and MPs harboring TF on their surface could in that way act on endothelial cells to promote vessel formation. Such MPs were shown to circulate in vivo (14), but their proangiogenic activity remains to be established, especially in a context in which the signaling activity of TF seems to be linked to its cytoplasmic domain, which is probably sequestered within MPs (7).

	Membrane Microparticles in Blood Coagulation

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 
Microparticles are essential for hemostasis
PS present at the surface of MPs provides a catalytic surface promoting the assembly of the characteristic enzyme complexes of the coagulation cascade. MPs shed from activated platelets constitute the main circulating population. They harbor major membrane glycoproteins, including functional adhesive receptors, and consequently disseminate a procoagulant potential that can be targeted according to the nature of counterligands (18). They can bind to soluble or immobilized fibrinogen and aggregate with platelets (26). The procoagulant potential of MPs is not, however, restricted to platelet MPs. MPs from monocytes, lymphocytes, or endothelial cells also present PS at their surface. Other effectors were also detected at the surface of circulating endothelial MPs, for instance von Willebrand factor and E-selectin (29).

Scott syndrome is the direct evidence of the key role of MPs and PS in hemostasis. This inherited disorder, characterized by hemorrhagic complications, is linked to the lack of surface exposure of plasma membrane PS and to the inability of platelets and other blood cells to generate MPs (49). Another bleeding disorder has also been described with decreased capacity of platelets to generate MPs, but at variance with Scott syndrome, with a correct PS exposure (13). These abnormalities highlight the importance of MPs in hemostasis and perhaps more particularly that of platelet MPs.

Microparticles and TF are closely associated in the vascular compartment
TF is the prime cellular initiator of coagulation. TF expression is not restricted to the subendothelium but can also originate from stimulated monocytes or endothelial cells (34). However, an essential point must be taken into account. At the stimulated monocyte cell surface only 10–20% of the total extractable TF activity is expressed. Thus there exists circulating, potentially active blood-borne TF in normal subjects, but most of its activity is latent or encrypted (22). TF activity is highly dependent on its lipid environment (5). Decryption could be mediated through the secretion of TF-rich MPs by monocytes. Such MPs can bind activated platelets or platelet-derived MPs and facilitate fusion events between monocytes (or monocyte MPs) and platelets (or platelet MPs) leading to MP rich in decrypted, active TF (42). Moreover, in experimental thrombi, TF was predominantly colocalized at the surface of membrane vesicles, frequently clustered adjacent to platelet surfaces (22).

Among the non-cell-bound TF present in blood, a variant form that results from alternative splicing of the primary RNA transcript was identified: alternatively spliced TF (asTF). asTF is soluble, circulates in plasma, and is biologically active. During thrombus formation, platelet deposition may separate catalytic enzyme complexes from circulating blood. Binding of asTF as well as TF-bearing monocyte-derived MPs to platelets provides a rationale for thrombus formation and growing (9). Binding can be mediated by platelet P-selectin and monocytic P-selectin glycoprotein ligand-1 (PSGL-1). This indicates one pathway for the initiation of blood coagulation involving the accumulation of TF-containing MPs in the platelet thrombus (15). The importance of the interaction between P-selectin and PSGL-1 was confirmed in vivo in a mouse model of hemophilia A in which soluble P-selectin was able to induce the generation of TF-positive MPs and correct hemostasis that way (27). Functional competence of blood-borne TF could be expressed when MPs and platelets adhere to neutrophils (40). Finally, in vitro interaction of endothelial MPs with monocytic cells was also shown to induce TF-dependent procoagulant activity (45).

Microparticles, thrombosis, and inflammation
It is obvious that pathological dysregulations leading to variations in the nature or proportion of circulating MPs (qualitative and quantitative aspects), and perhaps more frequently an augmentation of the number of circulating procoagulant MPs, will result in an increased thrombotic propensity. Elevated levels of circulating MPs have indeed been reported in various disorders characterized by thrombotic complications and more particularly in cardiovascular diseases (39, 51).

The implication of MPs in inflammation is also well documented. For instance, the presence of interleukin-1ß (IL-1ß) was observed in shed MPs (33), and MPs are a source of aminophospholipid substrates of secretory phospholipase A₂ for the generation of lysophosphatidic acid, a potent proinflammatory mediator and platelet agonist (17). Additionally, MPs were shown to favor endothelial activation and monocyte-endothelium interactions, the two initial steps of the atherosclerotic plaque formation (28). Blood-derived MPs can stimulate release of cytokines from endothelial cells and upregulation of TF expression at their surface (38). Platelet-derived MPs also enhanced expression of cell adhesion molecules in monocytic and endothelial cells and induced production of IL-8, IL-1ß, and IL-6 by endothelial cells as well as IL-8, IL-1ß, and tumor necrosis factor- by THP-1 cells (ATCC no. TIB-202) (41).

Together, these studies show that MPs are key actors of blood coagulation, but their pathophysiological role is clearly not restricted to their procoagulant potential.

	Membrane Microparticles in Immunity

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 
MP release is one of the early hallmarks of cells undergoing apoptosis, and shedding from senescent cells was shown to be correlated to the degree of apoptosis (4). It is therefore reasonable to consider that systems in charge of the elimination of cell waste products gain information from qualitative or quantitative variations of MPs.

Ectosomes and opsonization
Upon activation, neutrophils release MPs at the site of inflammation in vivo. These MPs, termed ectosomes, bind efficiently to opsonized bacteria and may be designed to focus antimicrobial activity onto opsonized surfaces (25). Ectosomes were also found to become specifically adherent to monocytic and endothelial cells, making them candidates for playing important roles in inflammation and cell signaling (20).

Ectosomes are thought to be released from the plasma membrane through the same mechanisms described above for MPs and also bear a significant proportion of PS. The centrifugation procedure used for their purification probably accounts for a selection of the smallest microvesicles present in the preparation (50–200 nm), thus possibly containing exosomes.

Immune escape mechanisms
MPs are suspected to support a sort of physiological immune escape as described in pregnancy. Since the invading trophoblast represents a semi-allograft, the mother should reject it. A very recent study proposes that secretion of FasL-containing MPs may constitute a mechanism by which trophoblast cells promote a state of immune privilege and, therefore, protect themselves from maternal immune recognition. Abrahams et al. (2) demonstrate that first-trimester trophoblast cells lack membrane-associated FasL but constitutively secrete FasL through the release of MPs, which, following MP disruption, is able to induce Fas-presenting T cell death by apoptosis.

Cancer is another situation in which MPs are implicated in escape from the immune system. A study shows that FasL-bearing MPs are shed in the extracellular medium by tumor cells and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells (3). In another study, epithelial ovarian cancer cells were shown to secrete functional FasL via the release of MPs (1). In contrast, normal ovarian epithelial cells express but do not secrete FasL. Together, these two studies suggest a mechanism by which tumors might neutralize Fas-bearing immune cells, thus facilitating escape and promoting survival.

Microparticles and AIDS
MPs seem to play several roles in AIDS, including implication in HIV infection, as well as in the propagation of the virus and its escape from classical vaccine strategies.

A few years ago, a mechanism allowing HIV to infect cells lacking the chemokine receptor CCR5 was suggested. CCR5 was released through MPs from the surface of CCR5-positive cells and was transferred to deficient peripheral blood mononuclear cells, rendering them CCR5 positive and susceptible to HIV-1 infection (32). A recent study confirms the existence of such a process by showing that platelet- and megakaryocyte-derived MPs can also transfer CXCR4 receptor to CXCR4-null cells (44).

In addition, one cannot exclude a role for CD4⁺-derived MPs observed in augmented proportions in some HIV-positive patients, especially in a situation in which individuals with high levels of circulating MPs and low circulating CD4⁺ cell counts seem to be protected from the classical complications of AIDS (4).

Microparticles and cancer
Like AIDS, cancer is a situation in which MPs are involved at different levels. For instance, monocyte-derived MPs were proposed to be a sign of vascular complication in patients with lung cancer, and elevated levels of circulating platelet MPs were observed in gastric cancer, with a possible role for MPs as metastasis predictors in the latter study (30, 31). Furthermore, doxorubicin was reported to accumulate in MPs shed by cancer cells, supporting the hypothesis that membrane vesiculation offers a way for tumors to rid themselves of toxic drugs, accounting in part for resistance to chemotherapy (46).

	Conclusion

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 
On the whole, these studies emphasize the increasing significance of MPs in fundamental physiological processes as well as under major pathological situations. They constitute the very first references for the interpretation of the role of MPs in physiology. Recent progress in the understanding of dynamic organization of the plasma membrane and the plasticity of its response should provide new bases for the identification of other biological functions for MPs in multicellular organisms.

	Acknowledgments

 
We apologize to all colleagues whose work could not be quoted owing to strict space constraints.

Research in our laboratory was supported by institutional funding from INSERM and the Université Louis Pasteur de Strasbourg, and by a grant from the Association "Vaincre la Mucoviscidose" awarded to M. Carmen Martínez.

	References

Top Introduction Mechanisms Governing the Plasma... Membrane Microparticles in... Membrane Microparticles in Blood... Membrane Microparticles in... Conclusion References

 

1. Abrahams VM, Straszewski SL, Kamsteeg M, Hanczaruk B, Schwartz PE, Rutherford TJ, and Mor G. Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res 63: 5573–5581, 2003.
2. Abrahams VM, Straszewski-Chavez SL, Guller S, and Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod 10: 55–63, 2004.
3. Albanese J, Meterissian S, Kontogiannea M, Dubreuil C, Hand A, Sorba S, and Dainiak N. Biologically active Fas antigen and its cognate ligand are expressed on plasma membrane-derived extracellular vesicles. Blood 91: 3862–3874, 1998.
4. Aupeix K, Hugel B, Martin T, Bischoff P, Lill H, Pasquali JL, and Freyssinet JM. The significance of shed membrane particles during programmed cell death in vitro and in vivo in HIV-1 infection. J Clin Invest 99: 1546–1554, 1997.
5. Bach R and Rifkin DB. Expression of tissue factor procoagulant activity: regulation by cytosolic calcium. Proc Natl Acad Sci USA 18: 6995–6999, 1990.
6. Baj-Krzyworzeka M, Majka M, Pratico D, Ratajczak J, Vilaire G, Kijowski J, Reca R, Janowska-Wieczorek A, and Ratajczak MZ. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp Hematol 30: 450–459, 2002.
7. Belting M, Dorrell MI, Sandgren S, Aguilar E, Ahamed J, Dorfleutner A, Carmeliet P, Mueller BM, Friedlander M, and Ruf W. Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. Nat Med 10: 502–509, 2004.
8. Bevers EM, Comfurius P, Dekkers DW, and Zwaal RF. Lipid translocation across the plasma membrane of mammalian cells. Biochim Biophys Acta 1439: 317–330, 1999.
9. Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, and Nemerson Y. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 9: 458–462, 2003.
10. Bose J, Gruber AD, Helming L, Schiebe S, Wegener I, Hafner M, Beales M, Kontgen F, and Lengeling A. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal. J Biol 3: 15, 2004.
11. Boulanger CM, Scoazec A, Ebrahimian T, Henry P, Mathieu E, Tedgui A, and Mallat Z. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 104: 2649–2652, 2001.
12. Brodsky SV, Zhang F, Nasjietti A, and Gollgorsky MS. Endothelium-derived microparticles impair endothelial function in vitro. Am J Physiol Heart Circ Physiol 286: H1910–H1915, 2004.
13. Castaman G, Yu-Feng L, Battistin E, and Rodeghiero F. Characterization of a novel bleeding disorder with isolated prolonged bleeding time and deficiency of platelet microvesicle generation. Br J Haematol 96: 458–463, 1997.
14. Diamant M, Nieuwland R, Pablo RF, Sturk A, Smit JW, and Radder JK. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 106: 2442–2447, 2002.
15. Falati S, Liu Q, Gross P, Merrill-Skoloff G, Chou J, Vandendries E, Celi A, Croce K, Furie BC, and Furie B. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med 197: 1585–1598, 2003.
16. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, and Raposo G. Cells release prions in association with exosomes. Proc Natl Acad Sci USA 101: 9683–9688, 2004.
17. Fourcade O, Simon MF, Viodé C, Rugani N, Leballe F, Ragad A, Fournié B, Sarda L, and Chap H. Secretory phospholipase A2 generates the novel lipid mediator lysophosphatidic acid in membrane microvesicles shed from activated cells. Cell 80: 919–927, 1995.
18. Fox JE. Shedding of adhesion receptors from the surface of activated platelets. Blood Coagul Fibrinolysis 5: 291–304, 1994.
19. Freyssinet JM. Cellular microparticles: what are they bad or good for? J Thromb Haemost 1: 1655–1662, 2003.
20. Gasser OS and Schifferli JA. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood. In press.
21. Gidon-Jeangirard C, Hugel B, Holl V, Toti F, Laplanche JL, Meyer D, and Freyssinet JM. Annexin V delays apoptosis while exerting an external constraint preventing the release of CD4+ and PrPc+ membrane particles in a human T lymphocyte model. J Immunol 162: 5712–5718, 1999.
22. Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, Badimon JJ, Himber J, Riederer MA, and Nemerson Y. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 96: 2311–2315, 1999.
23. Greco V, Hannus M, and Eaton S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106: 633–645, 2001.
24. Henderson RM, Edwardson JM, Geisse NA, and Saslowsky DE. Lipid rafts: feeling is believing. News Physiol Sci 19: 39–43, 2004.
25. Hess C, Sadallah S, Hefti A, Landmann R, and Schifferli JA. Ectosomes released by human neutrophils are specialized functional units. J Immunol 163: 4564–4573, 1999.
26. Holme PA, Solum NO, Brosstad F, Pedersen T, and Kveine M. Microvesicles bind soluble fibrinogen, adhere to immobilized fibrinogen and coaggregate with platelets. Thromb Haemost 79: 389–394, 1998.
27. Hrachovinova I, Cambien B, Hafezi-Moghadam A, Kappelmayer J, Camphausen RT, Widom A, Xia L, Kazazian HHJ, Schaub RG, McEver RP, and Wagner DD. Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med 9: 1020–1025, 2003.
28. Huber J, Vales A, Mitulovic G, Blumer M, Schmid R, Witztum JL, Binder BR, and Leitinger N. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler Thromb Vasc Biol 22: 101–107, 2002.
29. Jimenez JJ, Jy W, Mauro LM, Horstman LL, Soderland C, and Ahn YS. Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation. Br J Haematol 123: 896–902, 2003.
30. Kanazawa S, Nomura S, Kuwana M, Muramatsu M, Yamaguchi K, and Fukuhara S. Monocyte-derived microparticles may be a sign of vascular complication in patients with lung cancer. Lung Cancer 39: 145–149, 2003.
31. Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, Kim HK, Ryu KW, Bae JM, and Kim S. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 39: 184–191, 2003.
32. Mack M, Kleinschmidt A, Bruhl H, Klier C, Nelson PJ, Cihak J, Plachy J, Stangassinger M, Erfle V, and Schlondorff D. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med 6: 769–775, 2000.
33. MacKenzie A, Wilson HL, Kiss-Toth E, Dower SK, North RA, and Surprenant A. Rapid secretion of interleukin-1ß by microvesicle shedding. Immunity 15: 825–835, 2001.
34. Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 24: 1015–1022, 2004.
35. Madeo F, Frohlich E, and Frohlich KU. A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139: 729–734, 1997.
36. Martin S, Tesse A, Hugel B, Martinez MC, Morel O, Freyssinet JM, and Andriantsitohaina R. Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression. Circulation 109: 1653–1659, 2004.
37. Mesri M and Altieri DC. Endothelial cell activation by leukocyte microparticles. J Immunol 161: 4382–4387, 1998.
38. Mesri M and Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 274: 23111–23118, 1999.
39. Morel O, Toti F, Hugel B, and Freyssinet JM. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 11: 156–164, 2004.
40. Muller I, Klocke A, Alex M, Kotzsch M, Luther T, Morgenstern E, Zieseniss S, Zahler S, Preissner K, and Engelmann B. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 17: 476–478, 2003.
41. Nomura S, Tandon NN, Nakamura T, Cone J, Fukuhara S, and Kambayashi J. High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. Atherosclerosis 158: 277–287, 2001.
42. Osterud B. The role of platelets in decrypting monocyte tissue factor. Semin Hematol 38: 2–5, 2001.
43. Pfister SL. Role of platelet microparticles in the production of thromboxane by rabbit pulmonary artery. Hypertension 43: 428–433, 2004.
44. Rozmyslowicz T, Majka M, Kijowski J, Murphy SL, Conover DO, Poncz M, Ratajczak J, Gaulton GN, and Ratajczak MZ. Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 17: 33–42, 2003.
45. Sabatier F, Roux V, Anfosso F, Camoin L, Sampol J, and Dignat-George F. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 99: 3962–3970, 2002.
46. Shedden K, Xie XT, Chandaroy P, Chang YT, and Rosania GR. Expulsion of small molecules in vesicles shed by cancer cells association with gene expression and chemosensitivity profiles. Cancer Res 63: 4331–4337, 2003.
47. Tabibzadeh SS, Kong QF, and Kapur S. Passive acquisition of leukocyte proteins is associated with changes in phosphorylation of cellular proteins and cell-cell adhesion properties. Am J Pathol 145: 930–940, 1994.
48. Thery C, Zitvogel L, and Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2: 569–579, 2002.
49. Toti F, Satta N, Fressinaud E, Meyer D, and Freyssinet JM. Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder. Blood 87: 1409–1415, 1996.
50. Vanwijk MJ, Svedas E, Boer K, Nieuwland R, Vanbavel E, and Kublickiene KR. Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women. Am J Obstet Gynecol 187: 1686–1693, 2002.
51. VanWijk MJ, VanBavel E, Sturk A, and Nieuwland R. Microparticles in cardiovascular diseases. Cardiovasc Res 59: 277–287, 2003.

This article has been cited by other articles:

				S. Simoncini, M.-S. Njock, S. Robert, L. Camoin-Jau, J. Sampol, J.-R. Harle, C. Nguyen, F. Dignat-George, and F. Anfosso TRAIL/Apo2L Mediates the Release of Procoagulant Endothelial Microparticles Induced by Thrombin In Vitro: A Potential Mechanism Linking Inflammation and Coagulation Circ. Res., April 24, 2009; 104(8): 943 - 951. [Abstract] [Full Text] [PDF]

				L. Ayers, B. Ferry, S. Craig, D. Nicoll, J. R. Stradling, and M. Kohler Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea Eur. Respir. J., March 1, 2009; 33(3): 574 - 580. [Abstract] [Full Text] [PDF]

				D. Castellana, F. Zobairi, M. C. Martinez, M. A. Panaro, V. Mitolo, J.-M. Freyssinet, and C. Kunzelmann Membrane Microvesicles as Actors in the Establishment of a Favorable Prostatic Tumoral Niche: A Role for Activated Fibroblasts and CX3CL1-CX3CR1 Axis Cancer Res., February 1, 2009; 69(3): 785 - 793. [Abstract] [Full Text] [PDF]

				A. Agouni, A. H. Lagrue-Lak-Hal, P. H. Ducluzeau, H. A. Mostefai, C. Draunet-Busson, G. Leftheriotis, C. Heymes, M. C. Martinez, and R. Andriantsitohaina Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome Am. J. Pathol., October 1, 2008; 173(4): 1210 - 1219. [Abstract] [Full Text] [PDF]

				H. A. Mostefai, A. Agouni, N. Carusio, M. L. Mastronardi, C. Heymes, D. Henrion, R. Andriantsitohaina, and M. C. Martinez Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells J. Immunol., April 1, 2008; 180(7): 5028 - 5035. [Abstract] [Full Text] [PDF]

				A. Agouni, H. A. Mostefai, C. Porro, N. Carusio, J. Favre, V. Richard, D. Henrion, M. C. Martinez, and R. Andriantsitohaina Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release FASEB J, September 1, 2007; 21(11): 2735 - 2741. [Abstract] [Full Text] [PDF]

				C. M. Boulanger, N. Amabile, A. P. Guerin, B. Pannier, A. S. Leroyer, Z. Mallat, C. Nguyen, A. Tedgui, and G. M. London In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease Hypertension, April 1, 2007; 49(4): 902 - 908. [Abstract] [Full Text] [PDF]

				C. Moosbauer, E. Morgenstern, S. L. Cuvelier, D. Manukyan, K. Bidzhekov, S. Albrecht, P. Lohse, K. D. Patel, and B. Engelmann Eosinophils are a major intravascular location for tissue factor storage and exposure Blood, February 1, 2007; 109(3): 995 - 1002. [Abstract] [Full Text] [PDF]

				G. Chironi, A. Simon, B. Hugel, M. Del Pino, J. Gariepy, J.-M. Freyssinet, and A. Tedgui Circulating Leukocyte-Derived Microparticles Predict Subclinical Atherosclerosis Burden in Asymptomatic Subjects Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2775 - 2780. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (63) Citing Articles via Google Scholar Google Scholar Articles by Hugel, B. Articles by Freyssinet, J.-M. Search for Related Content PubMed PubMed Citation Articles by Hugel, B. Articles by Freyssinet, J.-M.