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Jeudi 19 Octobre 2017
Faculté de Médecine Université Paris Descartes - Institut National de la Transfusion Sanguine
Red Pulp Fiction: From mechanical sensing of red blood cells by the human spleen to the control of malaria
Filtration of red blood cells (RBC) by the human spleen can be either protective or harmful in several inherited and acquired red blood cell diseases in humans such as hereditary spherocytosis, sickle cell disease or malaria, amonst others. (1). Retention of infected RBC in the spleen likely slowers the pace of infection in malaria, removes potentially pathogenic RBC subpopulations in inherited RBC diseases but reduces the number of RBC in circulation, causing anemia. Abrupt pooling of RBC can contribute to increase the size of the spleen leading to rare but severe complications in malaria (spleen rupture) and sickle cell disease (2, acute splenic sequestration crises). Over the last 10 years, we have developed new tools to explore the filtering function of the spleen. Studies in malaria have confirmed the protective role of a functional spleen (3,4) and the pathogenic role of subpopulations of RBC in this acquired RBC disease (1). We have proposed a generic structure for the functional unit of the filtering spleen (1), the « splenon », that is amenable to experimental reconstruction (5). New tools, namely ex-vivo perfusion of human spleens (6), filtration of RBC through layers of microspheres (« microsphiltration ») (7), biomimetic microfluidic chips that mimic interendothelial slits in the human spleen (8), and morphological analysis of RBC using imaging flow cytometry (9,10) will be presented, along with their recent application to the exploration of RBC physiology and disease and the screening for new drugs to block the transmission of malaria (11,12,7). 1. Buffet PA, Safeukui I, Deplaine G, Brousse V, Prendki V, Thellier M, Turner G, Mercereau-Puijalon O. The pathogenesis of P. falciparum malaria in humans - Insights from spleen physiology. Blood 2011;117 :,381-392 2. Brousse V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol. 2014 Jul;166(2):165-76. doi: 10.1111/bjh.12950. 3. Safeukui I, Correas J-M, Brousse V, Hirt D, Deplaine G, Mulé S, Lesurtel M, Goasguen N, Sauvanet A, Couvelard A, Kerneis S, Khun H, Vigan-Womas I, Ottone C, Molina TJ, Tréluyer JM, Mercereau-Puijalon O, Milon G, David PH, Buffet PA. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open micro-circulation of the human spleen. Blood 2008;112:2520-28 4. Safeukui I, Buffet PA, Perrot S, Sauvanet A, Aussilhou B, Dokmak S, Couvelard, A Hatem, DC ; Mohandas, N ; David, PH ;Mercereau-Puijalon, O ; Milon, G Surface Area Loss and Increased Sphericity Account for the Splenic Entrapment of Subpopulations of Plasmodium falciparum Ring-Infected Erythrocytes PLoS One 2013;8(3): e60150 DOI:10.1371/journal.pone.0060150 5. Gambhire P, Atwell S, Iss C, Bedu F, Ozerov I, Badens C, Helfer E, Viallat A, Charrier A. High Aspect Ratio Sub-Micrometer Channels Using Wet Etching: Application to the Dynamics of Red Blood Cell Transiting through Biomimetic Splenic Slits. Small. 2017 Aug;13(32). doi: 10.1002/smll.201700967. Epub 2017 Jun 26. 6. Buffet PA, Milon G, Brousse V, Correas JM, Dousset B, Couvelard A, Kianmanesh R, Farges O, Sauvanet S, Paye F, Ungeheuer MN, Ottone C, Khun H, Fiette L, Huerre M, Mercereau-Puijalon O, David PH. Ex-vivo perfusion of human spleens maintains clearing and processing functions. Blood 2006;107(9):3745-52 7. Deplaine G, Safeukui I, Jeddi F, Lacoste F, Brousse V, Perrot S, Biligui S, Guillotte M, Guitton C, Dokmak S, Aussilhou B, Sauvanet A, Couvelard A, Paye F, Thellier M, Mazier D, Milon G, Mohandas N, Mercereau-Puijalon O, David PH, Buffet PA. The sensing of rigid red blood cells by the human spleen can be mimicked in vitro Blood 2011;117 (8), e88-e95 8. Picot J*, Ndour PA*, El Nemer W*, Tawfik H, Le Pioufle B, Buffet P, Le Van Kim C, Français O. A biomimetic microfluidic chip to study the circulation and mechanical retention of erythrocytes in the spleen. Am J Hematol 2015; Jan 12. doi: 10.1002/ajh.23941 9. Safeukui I, Buffet PA, Deplaine G, Perrot S, Brousse V, Ndour A, Nguyen M, Mercereau-Puijalon O, David PH, Milon G, Mohandas N. Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by human spleen: implications for understanding clinical variability of membrane disorders Blood 2012;120:424-30 10. Roussel C*, Dussiot M*, Marin M, Morel A, Ndour A, Duez J, Le Van Kim C, Hermine O, Colin Y, Buffet P*, Amireault P* Spherocytic shift of red blood cells during storage provides a quantitative whole cell-based marker of the storage lesion. Transfusion. In press 11 Diakité SAS, Ndour PA, Brousse V, Gay F, Roussel C, Biligui S, Dussiot M, Prendki V, Lopera-Mesa TM, Traoré K, Konaté D, Doumbia S, Cros J, Dokmak S, Fairhurst RM, Diakité M, Buffet PA. Stage-dependent fate of Plasmodium falciparum-infected red blood cells in the spleen and sickle-cell trait-related protection against malaria Malaria Journal 2016 ;15 (1), 482 12. Henry B, Roussel C, Ndour PA, Carucci M, Duez J, Fricot A, Aussenac F, Akpovi H, Courtin D, Clain J, Colin Aronovicz Y, Garcia A, Sabbagh A, Buffet PA. Red Blood Cell Deformability, Age, Ethnicity and Susceptibility to Malaria in Africa Blood 2016 ;128 (22), 2441-2441

Jeudi 14 Décembre 2017
Emilie Franceschini
LMA, Marseille