Megakaryocytes use in vivo podosome-like structures working collectively to penetrate the endothelial barrier of bone marrow sinusoids.
Arp2/3
endothelial cells
megakaryocyte
myosin IIA
podosomes
thrombopoiesis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
07
05
2020
revised:
18
06
2020
accepted:
16
07
2020
pubmed:
24
7
2020
medline:
15
5
2021
entrez:
24
7
2020
Statut:
ppublish
Résumé
Blood platelets are anucleate cell fragments that prevent bleeding and minimize blood vessel injury. They are formed from the cytoplasm of megakaryocytes located in the bone marrow. For successful platelet production, megakaryocyte fragments must pass through the sinusoid endothelial barrier by a cell biology process unique to these giant cells as compared with erythrocytes and leukocytes. Currently, the mechanisms by which megakaryocytes interact and progress through the endothelial cells are not understood, resulting in a significant gap in our knowledge of platelet production. The aim of this study was to investigate how megakaryocytes interact and progress through the endothelial cells of mouse bone marrow sinusoids. We used a combination of fluorescence, electron, and three-dimensional microscopy to characterize the cellular events between megakaryocytes and endothelial cells. We identified protrusive, F-actin-based podosome-like structures, called in vivo-MK podosomes, which initiate the formation of pores through endothelial cells. These structures present a collective and spatial organization through their interconnection via a contractile network of actomyosin, essential to regulate the endothelial openings. This ensures proper passage of megakaryocyte-derived processes into the blood circulation to promote thrombopoiesis. This study provides novel insight into the in vivo function of podosomes of megakaryocytes with critical importance to platelet production.
Sections du résumé
BACKGROUND
Blood platelets are anucleate cell fragments that prevent bleeding and minimize blood vessel injury. They are formed from the cytoplasm of megakaryocytes located in the bone marrow. For successful platelet production, megakaryocyte fragments must pass through the sinusoid endothelial barrier by a cell biology process unique to these giant cells as compared with erythrocytes and leukocytes. Currently, the mechanisms by which megakaryocytes interact and progress through the endothelial cells are not understood, resulting in a significant gap in our knowledge of platelet production.
OBJECTIVE
The aim of this study was to investigate how megakaryocytes interact and progress through the endothelial cells of mouse bone marrow sinusoids.
METHODS
We used a combination of fluorescence, electron, and three-dimensional microscopy to characterize the cellular events between megakaryocytes and endothelial cells.
RESULTS
We identified protrusive, F-actin-based podosome-like structures, called in vivo-MK podosomes, which initiate the formation of pores through endothelial cells. These structures present a collective and spatial organization through their interconnection via a contractile network of actomyosin, essential to regulate the endothelial openings. This ensures proper passage of megakaryocyte-derived processes into the blood circulation to promote thrombopoiesis.
CONCLUSION
This study provides novel insight into the in vivo function of podosomes of megakaryocytes with critical importance to platelet production.
Identifiants
pubmed: 32702204
doi: 10.1111/jth.15024
pii: S1538-7836(22)03714-X
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2987-3001Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM130312
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133668
Pays : United States
Informations de copyright
© 2020 International Society on Thrombosis and Haemostasis.
Références
Guo T, Wang X, Qu Y, Yin Y, Jing T, Zhang Q. Megakaryopoiesis and platelet production: insight into hematopoietic stem cell proliferation and differentiation. Stem Cell Investig. 2015;2:3.
Radley JM, Haller CJ. The demarcation membrane system of the megakaryocyte: a misnomer? Blood. 1982;60:213-219.
Schulze H, Korpal M, Hurov J, et al. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis. Blood. 2006;107:3868-3875.
Eckly A, Heijnen H, Pertuy F, et al. Biogenesis of the demarcation membrane system (DMS) in megakaryocytes. Blood. 2014;123:921-930.
Tavassoli M, Aoki M. Migration of entire megakaryocytes through the marrow-blood barrier. Br J Haematol. 1981;48:25-29.
Lefrancais E, Ortiz-Munoz G, Caudrillier A, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature. 2017;544:105-109.
Johnston I, Hayes V, Poncz M. Threading an elephant through the eye of a needle: where are platelets made? Cell Res. 2017;27:1079-1080.
Sabri S, Foudi A, Boukour S, et al. Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment. Blood. 2006;108:134-140.
Kahr WH, Pluthero FG, Elkadri A, et al. Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nat Commun. 2017;8:14816.
Lichtman MA, Chamberlain JK, Simon W, Santillo PA. Parasinusoidal location of megakaryocytes in marrow: a determinant of platelet release. Am J Hematol. 1978;4:303-312.
Scurfield G, Radley JM. Aspects of platelet formation and release. Am J Hematol. 1981;10:285-296.
Schachtner H, Calaminus SD, Sinclair A, et al. Megakaryocytes assemble podosomes that degrade matrix and protrude through basement membrane. Blood. 2013;121:2542-2552.
Linder S, Wiesner C. Feel the force: podosomes in mechanosensing. Exp Cell Res. 2016;343:67-72.
Nolen BJ, Tomasevic N, Russell A, et al. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nature. 2009;460:1031-1034.
Garcia E, Jones GE, Machesky LM, Anton IM. WIP: WASP-interacting proteins at invadopodia and podosomes. Eur J Cell Biol. 2012;91:869-877.
Tiedt R, Coers J, Ziegler S, et al. Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes. Blood. 2009;113:1768-1777.
Leon C, Eckly A, Hechler B, et al. Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion. Blood. 2007;110:3183-3191.
Paul DS, Casari C, Wu C, et al. Deletion of the Arp2/3 complex in megakaryocytes leads to microthrombocytopenia in mice. Blood Advan. 2017;1:1398-1408.
Micheva KD, O'Rourke N, Busse B, Smith SJ. Array tomography: high-resolution three-dimensional immunofluorescence. Cold Spring Harb Protoc. 2010;2010(11):1214-1218.
Eckly A, Strassel C, Cazenave JP, Lanza F, Leon C, Gachet C. Characterization of megakaryocyte development in the native bone marrow environment. Methods Mol Biol. 2012;788:175-192.
Eckly A, Rinckel JY, Proamer F, Gachet C. High-resolution 3D imaging of megakaryocytes using focused ion beam-scanning electron microscopy. Methods Mol Biol. 2018;1812:217-231.
Campbell FR. Intercellular contacts between migrating blood cells and cells of the sinusoidal wall of bone marrow. An ultrastructural study using tannic acid. Anat Rec. 1982;203:365-374.
Junt T, Schulze H, Chen Z, et al. Dynamic visualization of thrombopoiesis within bone marrow. Science. 2007;317:1767-1770.
Stegner D, vanEeuwijk JMM, Angay O, et al. Thrombopoiesis is spatially regulated by the bone marrow vasculature. Nat Commun. 2017;8:127.
Zhang L, Orban M, Lorenz M, et al. A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis. J Exp Med. 2012;209:2165-2181.
Eckly A, Strassel C, Freund M, et al. Abnormal megakaryocyte morphology and proplatelet formation in mice with megakaryocyte-restricted MYH9 inactivation. Blood. 2009;113:3182-3189.
Elmasri H, Karaaslan C, Teper Y, et al. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J. 2009;23:3865-3873.
Lee BS. Myosins in osteoclast formation and function. Biomolecules. 2018;8:157.
Labernadie A, Bouissou A, Delobelle P, et al. Protrusion force microscopy reveals oscillatory force generation and mechanosensing activity of human macrophage podosomes. Nat Commun. 2014;5:5343.
van den Dries K, Meddens MB, de Keijzer S, et al. Interplay between myosin IIA-mediated contractility and actin network integrity orchestrates podosome composition and oscillations. Nat Commun. 2013;4:1412.
Feng D, Nagy JA, Pyne K, Dvorak HF, Dvorak AM. Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med. 1998;187:903-915.
van den Dries K, Nahidiazar L, Slotman JA, et al. Modular actin nano-architecture enables podosome protrusion and mechanosensing. Nat Commun. 2019;10:5171.
Carman CV, Sage PT, Sciuto TE, et al. Transcellular diapedesis is initiated by invasive podosomes. Immunity. 2007;26:784-797.
Kelley LC, Chi Q, Caceres R, et al. Adaptive F-actin polymerization and localized ATP production drive basement membrane invasion in the absence of MMPs. Dev Cell. 2019;48(3):313-328.e8.
Rowe RG, Weiss SJ. Breaching the basement membrane: who, when and how? Trends Cell Biol. 2008;18:560-574.
Caceres R, Bojanala N, Kelley LC, et al. Forces drive basement membrane invasion in Caenorhabditis elegans. Proc Natl Acad Sci USA. 2018;115:11537-11542.
Lane WJ, Dias S, Hattori K, et al. Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood. 2000;96:4152-4159.
Malara A, Ligi D, Di Buduo CA, Mannello F, Balduini A. Sub-cellular localization of metalloproteinases in megakaryocytes. Cells. 2018;7:80.
Molinie N, Gautreau A. The Arp2/3 regulatory system and its deregulation in cancer. Physiol Rev. 2018;98:215-238.
Tablin F, Castro M, Leven RM. Blood platelet formation in vitro. The role of the cytoskeleton in megakaryocyte fragmentation. J Cell Sci. 1990;97(Pt 1):59-70.
Bornert A, Boscher J, Pertuy F, et al. Cytoskeletal-based mechanisms differently regulate in vivo and in vitro proplatelet formation. Haematologica. 2020;105. [epub ahead of print]. https://doi.org/10.3324/haematol.2019.239111
Bhuwania R, Cornfine S, Fang Z, Kruger M, Luna EJ, Linder S. Supervillin couples myosin-dependent contractility to podosomes and enables their turnover. J Cell Sci. 2012;125:2300-2314.
Meddens MB, Pandzic E, Slotman JA, et al. Actomyosin-dependent dynamic spatial patterns of cytoskeletal components drive mesoscale podosome organization. Nat Commun. 2016;7:13127.
Georgess D, Machuca-Gayet I, Blangy A, Jurdic P. Podosome organization drives osteoclast-mediated bone resorption. Cell Adh Migr. 2014;8:191-204.
Proag A, Bouissou A, Mangeat T, et al. Working together: spatial synchrony in the force and actin dynamics of podosome first neighbors. ACS Nano. 2015;9:3800-3813.
Becker RP, De Bruyn PPH. The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation. Am J Anat. 1976;145:183-205.
Lemichez E, Gonzalez-Rodriguez D, Bassereau P, Brochard-Wyart F. Transcellular tunnel dynamics: control of cellular dewetting by actomyosin contractility and I-BAR proteins. Biol Cell. 2013;105:109-117.