Received Date : 10-Mar-2014 Accepted Date : 11-Mar-2014
Accepted Article
Article type
: Commentary
Neutrophils as new conductors of vascular homeostasis David M. Smadja1,2,3
1) Université Paris Descartes, Sorbonne Paris Cité, Paris, France 2) Inserm UMR-S1140, Paris, France 3) AP-HP, Hôpital Européen Georges Pompidou, Hematology Department, Paris, France
Address for correspondence: Prof. David Smadja, Paris Descartes University, Hematology Department European Georges Pompidou Hospital 20 rue Leblanc, 75015 Paris, France Tel: +3156093933, Fax: +3156093393 E-Mail: [email protected]
Key words: Neutrophils, endothelial progenitor cells, ECFC, vessel injury, angiogenesis, NETs
Endothelial progenitor cells (EPC) and stem cells have therapeutic potential for the treatment of peripheral arterial disease (PAD) and acute coronary syndrome (ACS) (1). These cells are thought to act either by giving rise to new vessels in situ, or as helper cells to mature endothelial cells during the re-
endothelialisation process following vascular injury. Within the context of thrombosis, different EPC subtypes can be recruited to sites of vessel damage, and, depending on the model used, they have been shown to be either beneficial for thrombus resolution, or conversely to exhibit deleterious
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/jth.12585 This article is protected by copyright. All rights reserved.
thrombotic effects. Growth factors, platelets (2), fibrin (3) or thrombin (4) have been proposed as agents that drive EPC homing to the thrombus. There is, however, a need to ascertain the result of an EPC-
Accepted Article
based cell therapy in terms of vascular injury regeneration for each clinical situation. In this issue of Journal of Thrombosis and Haemostasis, Hubert et al. demonstrate for the first time (5) in a well-recognized cremaster arterial laser-induced injury model of thrombosis - that neutrophils that are present at the site of activated endothelial cells can recruit endothelial colony forming cells (ECFC), the vasculogenic type of EPC, without interfering with kinetics of thrombus formation (for easy reading, these cells will hereafter be termed EPC). The regenerative potential of EPC has been demonstrated in several preclinical models of ischemia or re-endothelialisation. EPC are also involved in thrombus recanalisation and resolution (6). Indeed, thrombi failed to resolve in urokinase-type plasminogen activator knockout mice, while wild-type mouse bone marrow–derived cells, potentially rich in progenitor cells, rescued thrombus re-organization and resolution in urokinase-type plasminogen activator deficient mice (7).
Bone marrow, peripheral blood mononuclear cells or mobilized progenitor cells administered in patients with ACS and PAD have shown efficacy in terms of cardiac function improvement and neoangiogenesis. However, aggravation of restenosis has also been described and could represent a major concern (8). In atherosclerosis, EPC involvement is contradictory. According to published data, EPC were shown either to increase or to reduce plaque size (9, 10), and even to revert cuff-induced thrombosis in ApoEdeficient mice (11). Interestingly, EPC express both hemostasis and fibrinolysis receptors/proteins that confer the ability to participate in coagulation. For instance, EPC express inducible tissue factor, inferring a strong thrombin generating potential, as well as surface thrombin receptors (12,13). Assessment of these procoagulant properties might therefore have clinical implications in the definition of EPC associated thrombogenic risk and delineation of possible strategies aimed at preventing adverse effects. Besides their procoagulant properties, EPC can activate protein C (4) and express the uPA/uPAR system (14), suggesting anticoagulant and fibrinolytic properties, respectively. Overall, implications of EPC in modulating thrombosis are unclear, and appear to depend upon the in vivo model used and cellular properties explored.
With respect to the ability of EPC to specifically home towards a thrombus, platelets (2), fibrin (3) and/or thrombin (4) have all been implicated. Although monocytes and some lymphocyte subpopulations control post-ischaemic vessel growth (15, 16), the influence of such inflammatory cells in EPC recruitment has not yet been explored. Cardiovascular patients who are eligible for cell-based therapy usually present with chronic inflammatory syndrome secondary to underlying diseases such as diabetes or other cardiovascular risk factors. EPC have been shown to be mobilized in response to inflammation and/or inflammatory cytokines, especially post angioplasty in PAD patients (17). Inflammatory cells may interfere with EPC recruitment.
This article is protected by copyright. All rights reserved.
The first cells recruited to activated endothelial cells during inflammation are neutrophils. Their main role is to rapidly migrate to sites of inflammation/infection in order to kill and degrade foreign bodies. A link
Accepted Article
between inflammation and thrombosis has been well recognized. Recently, several studies have suggested that neutrophils play a crucial role in thrombus formation. The group of Dr Dubois showed that neutrophils are the first cells accumulating at the site of arterial injury (18). Neutrophil depletion significantly decreases both thrombus formation and fibrin generation, suggesting that neutrophils contain molecules required to support the onset of the coagulation cascade mediated at least in part by tissue factor (18). Hubert et al. describe in this issue of JTH that neutrophils play a crucial role in EPC recruitment without affecting thrombus size, thus confirming the central involvement of neutrophils in vascular homeostasis. A link between EPC and neutrophils has been previously proposed by the group of Dr Bischoff in a matrigel implant model (19). Results presented here confirm the neutrophil/EPC interaction using a thrombosis model. More than just recruiting EPC, neutrophils seem to represent critical determinants of thrombus organization by recruiting both platelets (18) and EPC (5). However, interaction of neutrophils and EPC is evidenced here in a model that does not enable the analysis of the long term effect of EPC in thrombus resolution or recanalization. This, surely, represents the next step to elucidate. Moreover, neutrophils do not just recruit EPC: they also increase their angiogenic potential. This is a newly described mechanism through which neutrophils regulate and modulate angiogenesis in thrombotic disease.
Neutrophils have been previously described to regulate angiogenesis via two main pathways: generating high levels of reactive oxygen species (ROS) and releasing lysosomal proteinases. Both mechanisms seem to be preferentially antiangiogenic. Neutrophil proangiogenic effects and their cooperation with EPC biology, and especially in EPC related-thrombotic disorders, needs further evaluation in additional settings beyond this endothelial injury model to fully understand this phenomenon. This missing mechanistic link could perhaps come from neutrophil-released "neutrophil extracellular traps" (NETs). Indeed, involvement of neutrophils in thrombus formation has been recently related to NETs. Upon stimulation, neutrophils are able to generate extracellular material composed by chromatin and granule contents called NETs. These NETs play an important role in trapping and killing pathogens and they have been involved in thrombosis and its propagation via tissue factor or concentration of proteins involved in thrombosis such as vWF or fibronectin (20). NETs provide a scaffold for platelet and red blood cell adhesion and it is tempting to speculate that NETs could contribute to EPC recruitment as proposed in Figure 1. NETs could trap EPC in circulation, presenting PSGL1 to neutrophil L-selectin. This trapping could be efficient in thrombosis but also in ischemic diseases and cell therapy approach in general. Moreover, neutrophil contamination of the final cell product (buffy coat vs. ficoll gradient) could modify the efficacy of autologous bone marrow mononuclear cell therapy by trapping and modifying stem cell efficacy and angiogenic properties. In conclusion, do we have to modify how we teach hemostasis? The binding of neutrophils to injured endothelial cells is probably the first step leading to thrombus formation, fibrin generation and EPC
This article is protected by copyright. All rights reserved.
recruitment. Dr. Dubois' group fill a gap in our knowledge by identifying neutrophils as the main cell actor in thrombosis associated with the activated endothelium without exposure of the subendothelial milieu.
Accepted Article
Neutrophils are the first cells recruited to sites of thrombosis and allow platelet aggregation. They are now involved in EPC recruitment to sites of thrombosis without influencing either platelets or thrombin. These results have many potential consequences in endothelial repair in the context of inflammation and strengthen the links between thrombosis, inflammation and vascular cell therapy. New imaging technologies in thrombosis have allowed neutrophils to join platelets and endothelial cells as members of the cellular hemostasis family. This is probably just the beginning…
Sources of fundings: Author's Research is supported by INSERM, Paris Descartes University, Région Ile de France-CORDDIM (Domaine d'intérêt majeur Cardiovasculaire Obésité Rein Diabète) and CARIGEST foundation.
Disclosures: Author does not have any conflict of interest to declare.
Figure legend: Figure 1: Schematic of thrombus formation after endothelial injury. Neutrophils, after binding endothelial ICAM-1, allow directly the recruitment of platelet and endothelial progenitor cells. Netting neutrophils participate in platelet recruitment and could help to EPC recruitment to thrombus site.
References:
1.
Silvestre JS, Smadja DM, Levy BI. Postischemic revascularization: from cellular and molecular
mechanisms to clinical applications. Physiol Rev 2013; 93: 1743-802.
2.
Massberg S, Konrad I, Schurzinger K, Lorenz M, Schneider S, Zohlnhoefer D, Hoppe K,
Schiemann M, Kennerknecht E, Sauer S, Schulz C, Kerstan S, Rudelius M, Seidl S, Sorge F, Langer H, Peluso M, Goyal P, Vestweber D, Emambokus NR, et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203:
1221-33. 3.
de Boer HC, Verseyden C, Ulfman LH, Zwaginga JJ, Bot I, Biessen EA, Rabelink TJ, van
Zonneveld AJ. Fibrin and activated platelets cooperatively guide stem cells to a vascular injury and promote differentiation towards an endothelial cell phenotype. Arterioscler Thromb Vasc Biol 2006; 26: 1653-9. 4.
Smadja DM, Basire A, Amelot A, Conte A, Bieche I, Le Bonniec BF, Aiach M, Gaussem P.
Thrombin bound to a fibrin clot confers angiogenic and haemostatic properties on endothelial progenitor cells. J Cell Mol Med 2008; 12: 975-86.
5.
Hubert L, Darbousset R, Panicot-Dubois L, Robert S, Sabatier F, Fallague K, Dignat-George F,
Dubois C. Neutrophils recruit and activate Human Endothelial Colony Forming Cells at the site of vessel
This article is protected by copyright. All rights reserved.
injury via PSGL-1 and L-Selectin. Journal of Thrombosis and Haemostasis 2014; In press. 6.
Modarai B, Burnand KG, Sawyer B, Smith A. Endothelial progenitor cells are recruited into
Accepted Article
resolving venous thrombi. Circulation 2005; 111: 2645-53. 7.
Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boelhouwer B, Smith A. Failure of thrombus
to resolve in urokinase-type plasminogen activator gene-knockout mice: rescue by normal bone marrowderived cells. Circulation 2003; 107: 869-75. 8.
Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK, Kim YJ, Soo Lee D, Sohn DW, Han
KS, Oh BH, Lee MM, Park YB. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004; 363: 751-6. 9.
Porto ML, Lima LC, Pereira TM, Nogueira BV, Tonini CL, Campagnaro BP, Meyrelles SS,
Vasquez EC. Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice. Lipids Health Dis 2011; 10: 155. 10.
Silvestre JS, Gojova A, Brun V, Potteaux S, Esposito B, Duriez M, Clergue M, Le Ricousse-
Roussanne S, Barateau V, Merval R, Groux H, Tobelem G, Levy B, Tedgui A, Mallat Z. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003; 108: 2839-42. 11.
Lima LC, Porto ML, Campagnaro BP, Tonini CL, Nogueira BV, Pereira TM, Vasquez EC,
Meyrelles SS. Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice. Lipids Health Dis 2012; 11: 96.
12.
Smadja DM, Laurendeau I, Avignon C, Vidaud M, Aiach M, Gaussem P. The angiopoietin
pathway is modulated by PAR-1 activation on human endothelial progenitor cells. J Thromb Haemost 2006; 4: 2051-8. 13.
Cuccuini W, Poitevin S, Poitevin G, Dignat-George F, Cornillet-Lefebvre P, Sabatier F, Nguyen P.
Tissue factor up-regulation in proinflammatory conditions confers thrombin generation capacity to endothelial colony-forming cells without influencing non-coagulant properties in vitro. J Thromb Haemost 2010; 8: 2042-52. 14.
Basire A, Sabatier F, Ravet S, Lamy E, Mialhe A, Zabouo G, Paul P, Gurewich V, Sampol J,
Dignat-George F. High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors. Thromb Haemost 2006; 95: 678-88.
15.
Cochain C, Rodero MP, Vilar J, Recalde A, Richart AL, Loinard C, Zouggari Y, Guerin C, Duriez
M, Combadiere B, Poupel L, Levy BI, Mallat Z, Combadiere C, Silvestre JS. Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization. Cardiovasc Res 2010; 88: 186-95.
16.
Zouggari Y, Ait-Oufella H, Waeckel L, Vilar J, Loinard C, Cochain C, Recalde A, Duriez M, Levy
BI, Lutgens E, Mallat Z, Silvestre JS. Regulatory T cells modulate postischemic neovascularization. Circulation 2009; 120: 1415-25.
17.
Marboeuf P, Corseaux D, Mouquet F, Van Belle E, Jude B, Susen S. Inflammation triggers
This article is protected by copyright. All rights reserved.
colony forming endothelial cell mobilization after angioplasty in chronic lower limb ischemia. J Thromb Haemost 2008; 6: 195-7.
Accepted Article
18.
Darbousset R, Thomas GM, Mezouar S, Frere C, Bonier R, Mackman N, Renne T, Dignat-
George F, Dubois C, Panicot-Dubois L. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 2012; 120: 2133-43. 19.
Melero-Martin JM, De Obaldia ME, Allen P, Dudley AC, Klagsbrun M, Bischoff J. Host myeloid
cells are necessary for creating bioengineered human vascular networks in vivo. Tissue Eng Part A 2010; 16: 2457-66. 20.
Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood 2014; In press.
This article is protected by copyright. All rights reserved.
Accepted Article
Article type
: Commentary
Neutrophils as new conductors of vascular homeostasis David M. Smadja1,2,3
1) Université Paris Descartes, Sorbonne Paris Cité, Paris, France 2) Inserm UMR-S1140, Paris, France 3) AP-HP, Hôpital Européen Georges Pompidou, Hematology Department, Paris, France
Address for correspondence: Prof. David Smadja, Paris Descartes University, Hematology Department European Georges Pompidou Hospital 20 rue Leblanc, 75015 Paris, France Tel: +3156093933, Fax: +3156093393 E-Mail: [email protected]
Key words: Neutrophils, endothelial progenitor cells, ECFC, vessel injury, angiogenesis, NETs
Endothelial progenitor cells (EPC) and stem cells have therapeutic potential for the treatment of peripheral arterial disease (PAD) and acute coronary syndrome (ACS) (1). These cells are thought to act either by giving rise to new vessels in situ, or as helper cells to mature endothelial cells during the re-
endothelialisation process following vascular injury. Within the context of thrombosis, different EPC subtypes can be recruited to sites of vessel damage, and, depending on the model used, they have been shown to be either beneficial for thrombus resolution, or conversely to exhibit deleterious
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an 'Accepted Article', doi: 10.1111/jth.12585 This article is protected by copyright. All rights reserved.
thrombotic effects. Growth factors, platelets (2), fibrin (3) or thrombin (4) have been proposed as agents that drive EPC homing to the thrombus. There is, however, a need to ascertain the result of an EPC-
Accepted Article
based cell therapy in terms of vascular injury regeneration for each clinical situation. In this issue of Journal of Thrombosis and Haemostasis, Hubert et al. demonstrate for the first time (5) in a well-recognized cremaster arterial laser-induced injury model of thrombosis - that neutrophils that are present at the site of activated endothelial cells can recruit endothelial colony forming cells (ECFC), the vasculogenic type of EPC, without interfering with kinetics of thrombus formation (for easy reading, these cells will hereafter be termed EPC). The regenerative potential of EPC has been demonstrated in several preclinical models of ischemia or re-endothelialisation. EPC are also involved in thrombus recanalisation and resolution (6). Indeed, thrombi failed to resolve in urokinase-type plasminogen activator knockout mice, while wild-type mouse bone marrow–derived cells, potentially rich in progenitor cells, rescued thrombus re-organization and resolution in urokinase-type plasminogen activator deficient mice (7).
Bone marrow, peripheral blood mononuclear cells or mobilized progenitor cells administered in patients with ACS and PAD have shown efficacy in terms of cardiac function improvement and neoangiogenesis. However, aggravation of restenosis has also been described and could represent a major concern (8). In atherosclerosis, EPC involvement is contradictory. According to published data, EPC were shown either to increase or to reduce plaque size (9, 10), and even to revert cuff-induced thrombosis in ApoEdeficient mice (11). Interestingly, EPC express both hemostasis and fibrinolysis receptors/proteins that confer the ability to participate in coagulation. For instance, EPC express inducible tissue factor, inferring a strong thrombin generating potential, as well as surface thrombin receptors (12,13). Assessment of these procoagulant properties might therefore have clinical implications in the definition of EPC associated thrombogenic risk and delineation of possible strategies aimed at preventing adverse effects. Besides their procoagulant properties, EPC can activate protein C (4) and express the uPA/uPAR system (14), suggesting anticoagulant and fibrinolytic properties, respectively. Overall, implications of EPC in modulating thrombosis are unclear, and appear to depend upon the in vivo model used and cellular properties explored.
With respect to the ability of EPC to specifically home towards a thrombus, platelets (2), fibrin (3) and/or thrombin (4) have all been implicated. Although monocytes and some lymphocyte subpopulations control post-ischaemic vessel growth (15, 16), the influence of such inflammatory cells in EPC recruitment has not yet been explored. Cardiovascular patients who are eligible for cell-based therapy usually present with chronic inflammatory syndrome secondary to underlying diseases such as diabetes or other cardiovascular risk factors. EPC have been shown to be mobilized in response to inflammation and/or inflammatory cytokines, especially post angioplasty in PAD patients (17). Inflammatory cells may interfere with EPC recruitment.
This article is protected by copyright. All rights reserved.
The first cells recruited to activated endothelial cells during inflammation are neutrophils. Their main role is to rapidly migrate to sites of inflammation/infection in order to kill and degrade foreign bodies. A link
Accepted Article
between inflammation and thrombosis has been well recognized. Recently, several studies have suggested that neutrophils play a crucial role in thrombus formation. The group of Dr Dubois showed that neutrophils are the first cells accumulating at the site of arterial injury (18). Neutrophil depletion significantly decreases both thrombus formation and fibrin generation, suggesting that neutrophils contain molecules required to support the onset of the coagulation cascade mediated at least in part by tissue factor (18). Hubert et al. describe in this issue of JTH that neutrophils play a crucial role in EPC recruitment without affecting thrombus size, thus confirming the central involvement of neutrophils in vascular homeostasis. A link between EPC and neutrophils has been previously proposed by the group of Dr Bischoff in a matrigel implant model (19). Results presented here confirm the neutrophil/EPC interaction using a thrombosis model. More than just recruiting EPC, neutrophils seem to represent critical determinants of thrombus organization by recruiting both platelets (18) and EPC (5). However, interaction of neutrophils and EPC is evidenced here in a model that does not enable the analysis of the long term effect of EPC in thrombus resolution or recanalization. This, surely, represents the next step to elucidate. Moreover, neutrophils do not just recruit EPC: they also increase their angiogenic potential. This is a newly described mechanism through which neutrophils regulate and modulate angiogenesis in thrombotic disease.
Neutrophils have been previously described to regulate angiogenesis via two main pathways: generating high levels of reactive oxygen species (ROS) and releasing lysosomal proteinases. Both mechanisms seem to be preferentially antiangiogenic. Neutrophil proangiogenic effects and their cooperation with EPC biology, and especially in EPC related-thrombotic disorders, needs further evaluation in additional settings beyond this endothelial injury model to fully understand this phenomenon. This missing mechanistic link could perhaps come from neutrophil-released "neutrophil extracellular traps" (NETs). Indeed, involvement of neutrophils in thrombus formation has been recently related to NETs. Upon stimulation, neutrophils are able to generate extracellular material composed by chromatin and granule contents called NETs. These NETs play an important role in trapping and killing pathogens and they have been involved in thrombosis and its propagation via tissue factor or concentration of proteins involved in thrombosis such as vWF or fibronectin (20). NETs provide a scaffold for platelet and red blood cell adhesion and it is tempting to speculate that NETs could contribute to EPC recruitment as proposed in Figure 1. NETs could trap EPC in circulation, presenting PSGL1 to neutrophil L-selectin. This trapping could be efficient in thrombosis but also in ischemic diseases and cell therapy approach in general. Moreover, neutrophil contamination of the final cell product (buffy coat vs. ficoll gradient) could modify the efficacy of autologous bone marrow mononuclear cell therapy by trapping and modifying stem cell efficacy and angiogenic properties. In conclusion, do we have to modify how we teach hemostasis? The binding of neutrophils to injured endothelial cells is probably the first step leading to thrombus formation, fibrin generation and EPC
This article is protected by copyright. All rights reserved.
recruitment. Dr. Dubois' group fill a gap in our knowledge by identifying neutrophils as the main cell actor in thrombosis associated with the activated endothelium without exposure of the subendothelial milieu.
Accepted Article
Neutrophils are the first cells recruited to sites of thrombosis and allow platelet aggregation. They are now involved in EPC recruitment to sites of thrombosis without influencing either platelets or thrombin. These results have many potential consequences in endothelial repair in the context of inflammation and strengthen the links between thrombosis, inflammation and vascular cell therapy. New imaging technologies in thrombosis have allowed neutrophils to join platelets and endothelial cells as members of the cellular hemostasis family. This is probably just the beginning…
Sources of fundings: Author's Research is supported by INSERM, Paris Descartes University, Région Ile de France-CORDDIM (Domaine d'intérêt majeur Cardiovasculaire Obésité Rein Diabète) and CARIGEST foundation.
Disclosures: Author does not have any conflict of interest to declare.
Figure legend: Figure 1: Schematic of thrombus formation after endothelial injury. Neutrophils, after binding endothelial ICAM-1, allow directly the recruitment of platelet and endothelial progenitor cells. Netting neutrophils participate in platelet recruitment and could help to EPC recruitment to thrombus site.
References:
1.
Silvestre JS, Smadja DM, Levy BI. Postischemic revascularization: from cellular and molecular
mechanisms to clinical applications. Physiol Rev 2013; 93: 1743-802.
2.
Massberg S, Konrad I, Schurzinger K, Lorenz M, Schneider S, Zohlnhoefer D, Hoppe K,
Schiemann M, Kennerknecht E, Sauer S, Schulz C, Kerstan S, Rudelius M, Seidl S, Sorge F, Langer H, Peluso M, Goyal P, Vestweber D, Emambokus NR, et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203:
1221-33. 3.
de Boer HC, Verseyden C, Ulfman LH, Zwaginga JJ, Bot I, Biessen EA, Rabelink TJ, van
Zonneveld AJ. Fibrin and activated platelets cooperatively guide stem cells to a vascular injury and promote differentiation towards an endothelial cell phenotype. Arterioscler Thromb Vasc Biol 2006; 26: 1653-9. 4.
Smadja DM, Basire A, Amelot A, Conte A, Bieche I, Le Bonniec BF, Aiach M, Gaussem P.
Thrombin bound to a fibrin clot confers angiogenic and haemostatic properties on endothelial progenitor cells. J Cell Mol Med 2008; 12: 975-86.
5.
Hubert L, Darbousset R, Panicot-Dubois L, Robert S, Sabatier F, Fallague K, Dignat-George F,
Dubois C. Neutrophils recruit and activate Human Endothelial Colony Forming Cells at the site of vessel
This article is protected by copyright. All rights reserved.
injury via PSGL-1 and L-Selectin. Journal of Thrombosis and Haemostasis 2014; In press. 6.
Modarai B, Burnand KG, Sawyer B, Smith A. Endothelial progenitor cells are recruited into
Accepted Article
resolving venous thrombi. Circulation 2005; 111: 2645-53. 7.
Singh I, Burnand KG, Collins M, Luttun A, Collen D, Boelhouwer B, Smith A. Failure of thrombus
to resolve in urokinase-type plasminogen activator gene-knockout mice: rescue by normal bone marrowderived cells. Circulation 2003; 107: 869-75. 8.
Kang HJ, Kim HS, Zhang SY, Park KW, Cho HJ, Koo BK, Kim YJ, Soo Lee D, Sohn DW, Han
KS, Oh BH, Lee MM, Park YB. Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet 2004; 363: 751-6. 9.
Porto ML, Lima LC, Pereira TM, Nogueira BV, Tonini CL, Campagnaro BP, Meyrelles SS,
Vasquez EC. Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice. Lipids Health Dis 2011; 10: 155. 10.
Silvestre JS, Gojova A, Brun V, Potteaux S, Esposito B, Duriez M, Clergue M, Le Ricousse-
Roussanne S, Barateau V, Merval R, Groux H, Tobelem G, Levy B, Tedgui A, Mallat Z. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003; 108: 2839-42. 11.
Lima LC, Porto ML, Campagnaro BP, Tonini CL, Nogueira BV, Pereira TM, Vasquez EC,
Meyrelles SS. Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice. Lipids Health Dis 2012; 11: 96.
12.
Smadja DM, Laurendeau I, Avignon C, Vidaud M, Aiach M, Gaussem P. The angiopoietin
pathway is modulated by PAR-1 activation on human endothelial progenitor cells. J Thromb Haemost 2006; 4: 2051-8. 13.
Cuccuini W, Poitevin S, Poitevin G, Dignat-George F, Cornillet-Lefebvre P, Sabatier F, Nguyen P.
Tissue factor up-regulation in proinflammatory conditions confers thrombin generation capacity to endothelial colony-forming cells without influencing non-coagulant properties in vitro. J Thromb Haemost 2010; 8: 2042-52. 14.
Basire A, Sabatier F, Ravet S, Lamy E, Mialhe A, Zabouo G, Paul P, Gurewich V, Sampol J,
Dignat-George F. High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors. Thromb Haemost 2006; 95: 678-88.
15.
Cochain C, Rodero MP, Vilar J, Recalde A, Richart AL, Loinard C, Zouggari Y, Guerin C, Duriez
M, Combadiere B, Poupel L, Levy BI, Mallat Z, Combadiere C, Silvestre JS. Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization. Cardiovasc Res 2010; 88: 186-95.
16.
Zouggari Y, Ait-Oufella H, Waeckel L, Vilar J, Loinard C, Cochain C, Recalde A, Duriez M, Levy
BI, Lutgens E, Mallat Z, Silvestre JS. Regulatory T cells modulate postischemic neovascularization. Circulation 2009; 120: 1415-25.
17.
Marboeuf P, Corseaux D, Mouquet F, Van Belle E, Jude B, Susen S. Inflammation triggers
This article is protected by copyright. All rights reserved.
colony forming endothelial cell mobilization after angioplasty in chronic lower limb ischemia. J Thromb Haemost 2008; 6: 195-7.
Accepted Article
18.
Darbousset R, Thomas GM, Mezouar S, Frere C, Bonier R, Mackman N, Renne T, Dignat-
George F, Dubois C, Panicot-Dubois L. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 2012; 120: 2133-43. 19.
Melero-Martin JM, De Obaldia ME, Allen P, Dudley AC, Klagsbrun M, Bischoff J. Host myeloid
cells are necessary for creating bioengineered human vascular networks in vivo. Tissue Eng Part A 2010; 16: 2457-66. 20.
Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood 2014; In press.
This article is protected by copyright. All rights reserved.
