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Journal articles
Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease
S. M. Camus
1
J. A. de Moraes
1
P. Bonnin
2
P. Abbyad
3
S. Le Jeune
4
F. Lionnet
5
L. Loufrani
6, 7
L. Grimaud
6, 7
J.-C. Lambry
8
D. Charue
1
L. Kiger
9
J.-M. Renard
1
C. Larroque
10
H. Le Clesiau
10
A. Tedgui
1
P. Bruneval
1
C. Barja-Fidalgo
A. Alexandrou
3
P.-L. Tharaux
1
C. M. Boulanger
1
O. P. Blanc-Brude
1
J.-C. Lambry 8
Author IdHAL : jean-christophe-lambry ORCID : https://orcid.org/0000-0001-8264-0391
D. Charue 1
Author
L. Kiger 9
Author
J.-M. Renard 1
Author
O. P. Blanc-Brude 1
Author
1
PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire (56 rue Leblanc
75015 PARIS
FRANCE - France)
- HEGP - Hôpital Européen Georges Pompidou [APHP] : U970 (20, rue Leblanc, 75015 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : UMR_S 970 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U970 (101, rue de Tolbiac, 75013 Paris - France)
2
CART U965 - Carcinose Angiogenèse et Recherche Translationnelle ; Angiogenese et recherche translationnelle (Hôpital Lariboisière 41 Bld de la Chapelle 75475 PARIS Cedex 10 - France)
- UPD7 - Université Paris Diderot - Paris 7 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U965 (101, rue de Tolbiac, 75013 Paris - France)
3
LOB - Laboratoire d'optique et biosciences (Route de Saclay 91128 PALAISEAU CEDEX - France)
- X - École polytechnique (École polytechnique, 91128 Palaiseau Cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U696 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7645 (France)
4
Hôpital avicenne (125, rue de Stalingrad 93000 Bobigny - France)
5
CHU Tenon [APHP] (4 Rue de la Chine, 75020 Paris - France)
6
BNMI - Biologie Neurovasculaire et Mitochondriale Intégrée (France)
- CNRS - Centre National de la Recherche Scientifique (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale (101, rue de Tolbiac, 75013 Paris - France)
- UA - Université d'Angers (Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01 - France)
7
CHU Angers - Centre Hospitalier Universitaire d'Angers (4 rue Larrey - 49933 Angers cedex 9 - France)
8
LOB - Laboratoire d'Optique et Biosciences (Ecole Polytechnique
91128 PALAISEAU Cedex - France)
- X - École polytechnique (École polytechnique, 91128 Palaiseau Cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1182 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7645 (France)
9
Hôpital Henri Mondor (Créteil - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôpital Henri Mondor (France)
- UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (61 avenue du Général de Gaulle - 94010 Créteil cedex - France)
Abstract : Intravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that hemeladen MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of hemeladen MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD.
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Journal articles
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https://hal-polytechnique.archives-ouvertes.fr/hal-01186628
Contributor : Denis Roura <>
Submitted on : Tuesday, August 25, 2015 - 1:22:21 PM
Last modification on : Tuesday, October 6, 2020 - 2:32:02 PM
Contributor : Denis Roura <>
Submitted on : Tuesday, August 25, 2015 - 1:22:21 PM
Last modification on : Tuesday, October 6, 2020 - 2:32:02 PM
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- HAL Id : hal-01186628, version 1
- DOI : 10.1182/blood-2014-07-589283
Collections
X | CNRS | UNIV-ANGERS | X-LOB | UNAM | UNIV-PARIS5 | UNIV-PARIS13 | UPEC-UPEM | USPC | UNIV-PARIS-SACLAY | X-DEP-BIO | UNIV-PARIS7 | UPEC | UNIV-PARIS | UP-SANTE
Citation
S. M. Camus, J. A. de Moraes, P. Bonnin, P. Abbyad, S. Le Jeune, et al.. Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease. Blood, American Society of Hematology, 2015, 125 (24), pp.3805-3814. ⟨10.1182/blood-2014-07-589283⟩. ⟨hal-01186628⟩
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