{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:57:57Z","timestamp":1791352677144,"version":"4.3.1"},"reference-count":28,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The current paradigm in the pathogenesis of several hemolytic red blood cell disorders is that reduced cellular deformability is a key determinant of splenic sequestration of affected red cells. Three distinct features regulate cellular deformability: membrane deformability, surface area-to-volume ratio (cell sphericity), and cytoplasmic viscosity. By perfusing normal human spleens ex vivo, we had previously showed that red cells with increased sphericity are rapidly sequestered by the spleen. Here, we assessed the retention kinetics of red cells with decreased membrane deformability but without marked shape changes. A controlled decrease in membrane deformability (increased membrane rigidity) was induced by treating normal red cells with increasing concentrations of diamide. Following perfusion, diamide-treated red blood cells (RBCs) were rapidly retained in the spleen with a mean clearance half-time of 5.9 minutes (range, 4.0-13.0). Splenic clearance correlated positively with increased membrane rigidity (r = 0.93; P &amp;lt; .0001). To determine to what extent this increased retention was related to mechanical blockade in the spleen, diamide-treated red cells were filtered through microsphere layers that mimic the mechanical sensing of red cells by the spleen. Diamide-treated red cells were retained in the microsphilters (median, 7.5%; range, 0%-38.6%), although to a lesser extent compared with the spleen (median, 44.1%; range, 7.3%-64.0%; P &amp;lt; .0001). Taken together, these results have implications for understanding the sensitivity of the human spleen to sequester red cells with altered cellular deformability due to various cellular alterations and for explaining clinical heterogeneity of RBC membrane disorders.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018024562","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T11:51:05Z","timestamp":1539172265000},"page":"2581-2587","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":71,"title":["Sensing of red blood cells with decreased membrane deformability by the human spleen"],"prefix":"10.1182","volume":"2","author":[{"given":"Innocent","family":"Safeukui","sequence":"first","affiliation":[{"name":"Immunologie Mol\u00e9culaire des Parasites, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France;"},{"name":"Centre national de la recherche scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France;"},{"name":"Boler-Parseghian Center for Rare and Neglected Diseases and"},{"name":"Department of Biological Sciences, University of Notre Dame, Notre Dame, IN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre A.","family":"Buffet","sequence":"additional","affiliation":[{"name":"INSERM\u2013University Pierre and Marie Curie (Paris 6 University) Unit\u00e9s Mixtes de Recherche Scientifique 945, Paris, France;"},{"name":"Department of Parasitology, Piti\u00e9 Salp\u00e9tri\u00e8re Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Deplaine","sequence":"additional","affiliation":[{"name":"Immunologie Mol\u00e9culaire des Parasites, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France;"},{"name":"Centre national de la recherche scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France;"},{"name":"INSERM\u2013University Pierre and Marie Curie (Paris 6 University) Unit\u00e9s Mixtes de Recherche Scientifique 945, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Perrot","sequence":"additional","affiliation":[{"name":"Immunologie Mol\u00e9culaire des Parasites, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France;"},{"name":"Centre national de la recherche scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Brousse","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Necker Hospital, AP-HP, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sauvanet","sequence":"additional","affiliation":[{"name":"Department of Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Aussilhou","sequence":"additional","affiliation":[{"name":"Department of Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safi","family":"Dokmak","sequence":"additional","affiliation":[{"name":"Department of Surgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Couvelard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beaujon Hospital, AP-HP, Clichy, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Cazals-Hatem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beaujon Hospital, AP-HP, Clichy, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Mercereau-Puijalon","sequence":"additional","affiliation":[{"name":"Immunologie Mol\u00e9culaire des Parasites, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France;"},{"name":"Centre national de la recherche scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Milon","sequence":"additional","affiliation":[{"name":"Immunophysiologie et Parasitisme, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"David","sequence":"additional","affiliation":[{"name":"Immunologie Mol\u00e9culaire des Parasites, D\u00e9partement de Parasitologie Mycologie, Institut Pasteur, Paris, France;"},{"name":"Centre national de la recherche scientifique, Unit\u00e9 de Recherche Associ\u00e9e 2581, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narla","family":"Mohandas","sequence":"additional","affiliation":[{"name":"New York Blood Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2018,10,10]]},"reference":[{"issue":"4","key":"2020021108382560300_B1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1182\/blood.V41.4.529.529","article-title":"The role of the sinus wall in the passage of erythrocytes through the spleen","volume":"41","author":"Chen","year":"1973","journal-title":"Blood"},{"issue":"8","key":"2020021108382560300_B2","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1182\/blood-2010-10-312801","article-title":"The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro","volume":"117","author":"Deplaine","year":"2011","journal-title":"Blood"},{"issue":"3","key":"2020021108382560300_B3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1172\/JCI109888","article-title":"Analysis of factors regulating erythrocyte deformability","volume":"66","author":"Mohandas","year":"1980","journal-title":"J Clin Invest"},{"issue":"5","key":"2020021108382560300_B4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1182\/blood.V61.5.899.899","article-title":"Osmotic gradient ektacytometry: comprehensive characterization of red cell volume and surface maintenance","volume":"61","author":"Clark","year":"1983","journal-title":"Blood"},{"issue":"2","key":"2020021108382560300_B5","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2012-01-404103","article-title":"Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen","volume":"120","author":"Safeukui","year":"2012","journal-title":"Blood"},{"issue":"3","key":"2020021108382560300_B6","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2141.2008.07091.x","article-title":"Disorders of red cell membrane","volume":"141","author":"An","year":"2008","journal-title":"Br J Haematol"},{"issue":"10","key":"2020021108382560300_B7","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1182\/blood-2008-07-161166","article-title":"Red cell membrane: past, present, and future","volume":"112","author":"Mohandas","year":"2008","journal-title":"Blood"},{"issue":"6","key":"2020021108382560300_B8","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1182\/blood.V63.6.1385.1385","article-title":"Rigid membranes of Malayan ovalocytes: a likely genetic barrier against malaria","volume":"63","author":"Mohandas","year":"1984","journal-title":"Blood"},{"issue":"4","key":"2020021108382560300_B9","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1083\/jcb.98.4.1348","article-title":"Decreased membrane deformability in Melanesian ovalocytes from Papua New Guinea","volume":"98","author":"Saul","year":"1984","journal-title":"J Cell Biol"},{"issue":"6","key":"2020021108382560300_B10","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1182\/blood.V74.6.2194.2194","article-title":"Cellular and membrane properties of alpha and beta thalassemic erythrocytes are different: implication for differences in clinical manifestations","volume":"74","author":"Schrier","year":"1989","journal-title":"Blood"},{"issue":"2","key":"2020021108382560300_B11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-2141.1999.01367.x","article-title":"Red cell deformability, splenic function and anaemia in thalassaemia","volume":"105","author":"Dondorp","year":"1999","journal-title":"Br J Haematol"},{"issue":"9","key":"2020021108382560300_B12","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1182\/blood-2005-10-4094","article-title":"Ex vivo perfusion of human spleens maintains clearing and processing functions","volume":"107","author":"Buffet","year":"2006","journal-title":"Blood"},{"issue":"6","key":"2020021108382560300_B13","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1182\/blood-2008-03-146779","article-title":"Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen","volume":"112","author":"Safeukui","year":"2008","journal-title":"Blood"},{"issue":"3","key":"2020021108382560300_B14","first-page":"539","article-title":"Stabilization of erythrocyte shape by a chemical increase in membrane shear stiffness","volume":"6","author":"Haest","year":"1980","journal-title":"Blood Cells"},{"issue":"3-4","key":"2020021108382560300_B15","first-page":"277","article-title":"Clinical potential of in vitro measured red cell deformability, a myth?","volume":"21","author":"Hardeman","year":"1999","journal-title":"Clin Hemorheol Microcirc"},{"issue":"3","key":"2020021108382560300_B16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/jss.400090315","article-title":"Bilayer balance and regulation of red cell shape changes","volume":"9","author":"Mohandas","year":"1978","journal-title":"J Supramol Struct"},{"issue":"8","key":"2020021108382560300_B17","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0022-2275(20)38048-2","article-title":"Interaction of cholesterol and lysophosphatidylcholine in determining red cell shape","volume":"23","author":"Lange","year":"1982","journal-title":"J Lipid Res"},{"issue":"4","key":"2020021108382560300_B18","doi-asserted-by":"crossref","first-page":"C970","DOI":"10.1152\/ajpcell.2000.279.4.C970","article-title":"Adaptation and survival of surface-deprived red blood cells in mice","volume":"279","author":"Murdock","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"issue":"4","key":"2020021108382560300_B19","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1172\/JCI101847","article-title":"The osmotic resistance (fragility) of human red cells","volume":"26","author":"Parpart","year":"1947","journal-title":"J Clin Invest"},{"issue":"7","key":"2020021108382560300_B20","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1182\/blood.V74.7.2562.2562","article-title":"Membrane deformability and the capacity for shape change in the erythrocyte","volume":"74","author":"Chasis","year":"1989","journal-title":"Blood"},{"issue":"3","key":"2020021108382560300_B21","doi-asserted-by":"crossref","first-page":"e60150","DOI":"10.1371\/journal.pone.0060150","article-title":"Surface area loss and increased sphericity account for the splenic entrapment of subpopulations of Plasmodium falciparum ring-infected erythrocytes","volume":"8","author":"Safeukui","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"2020021108382560300_B22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0005-2736(94)90087-6","article-title":"Binding of naturally occurring antibodies to oxidatively and nonoxidatively modified erythrocyte band 3","volume":"1190","author":"Turrini","year":"1994","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"2020021108382560300_B23","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1046\/j.1365-2141.2001.02707.x","article-title":"Growth of Plasmodium falciparum induces stage-dependent haemichrome formation, oxidative aggregation of band 3, membrane deposition of complement and antibodies, and phagocytosis of parasitized erythrocytes","volume":"113","author":"Giribaldi","year":"2001","journal-title":"Br J Haematol"},{"issue":"21","key":"2020021108382560300_B24","doi-asserted-by":"crossref","first-page":"7368","DOI":"10.1073\/pnas.84.21.7368","article-title":"Naturally occurring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes","volume":"84","author":"Lutz","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"issue":"36","key":"2020021108382560300_B25","doi-asserted-by":"crossref","first-page":"21711","DOI":"10.1016\/S0021-9258(20)88244-1","article-title":"Platelet-activating factor enhances complement-dependent phagocytosis of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1)","volume":"264","author":"Bussolino","year":"1989","journal-title":"J Biol Chem"},{"issue":"3","key":"2020021108382560300_B26","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1182\/blood-2014-06-585299","article-title":"Cell rigidity and shape override CD47's \u201cself\u201d-signaling in phagocytosis by hyperactivating myosin-II","volume":"125","author":"Sosale","year":"2015","journal-title":"Blood"},{"issue":"1","key":"2020021108382560300_B27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/BF00582630","article-title":"Is \u201cdeformability\u201d a parameter for the rate of elimination of erythrocytes from the circulation?","volume":"388","author":"Haest","year":"1980","journal-title":"Pflugers Arch"},{"issue":"5","key":"2020021108382560300_B28","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1172\/JCI109964","article-title":"Decreased survival in vivo of diamide-incubated dog erythrocytes. A model of oxidant-induced hemolysis","volume":"66","author":"Johnson","year":"1980","journal-title":"J Clin Invest"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/20\/2581\/1629596\/advances024562.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/20\/2581\/1629596\/advances024562.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T02:25:08Z","timestamp":1720664708000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/2\/20\/2581\/16117\/Sensing-of-red-blood-cells-with-decreased-membrane"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,10]]},"references-count":28,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2018,10,23]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2018024562","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,10]]}}}