title: The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro.
abstract: Retention of poorly deformable red blood cells (RBCs) by the human spleen has been recognized as a critical determinant of pathogenesis in hereditary spherocytosis, malaria, and other RBC disorders. Using an ex vivo perfusion system, we had previously shown that retention of Plasmodium falciparum-infected RBCs (Pf-RBCs) occur in the splenic red pulp, upstream from the sinus wall. To experimentally replicate the mechanical sensing of RBCs by the splenic microcirculation, we designed a sorting device where a mixture of 5- to 25-μm-diameter microbeads mimics the geometry of narrow and short interendothelial splenic slits. Heated RBCs, Pf-RBCs, and RBCs from patients with hereditary spherocytosis were retained in the microbead layer, without hemolysis. The retention rates of Pf-RBCs were similar in microbeads and in isolated perfused human spleens. These in vitro results directly confirm the importance of the mechanical sensing of RBCs by the human spleen. In addition, rigid and deformable RBC subpopulations could be separated and characterized at the molecular level, and the device was used to deplete a stored RBC population from its subpopulation of rigid RBCs. This experimental approach may contribute to a better understanding of the role of the spleen in the pathogenesis of inherited and acquired RBC disorders.
authors.affiliation: Unité d'Immunologie Moléculaire des Parasites, Département de Parasitologie Mycologie, Institut Pasteur, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deplaine
authors.forename: Innocent
authors.initials: I
authors.lastname: Safeukui
authors.forename: Fakhri
authors.initials: F
authors.lastname: Jeddi
authors.forename: François
authors.initials: F
authors.lastname: Lacoste
authors.forename: Valentine
authors.initials: V
authors.lastname: Brousse
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perrot
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Biligui
authors.forename: Micheline
authors.initials: M
authors.lastname: Guillotte
authors.forename: Corinne
authors.initials: C
authors.lastname: Guitton
authors.forename: Safi
authors.initials: S
authors.lastname: Dokmak
authors.forename: Béatrice
authors.initials: B
authors.lastname: Aussilhou
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals Hatem
authors.forename: François
authors.initials: F
authors.lastname: Paye
authors.forename: Marc
authors.initials: M
authors.lastname: Thellier
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
mesh_terms: D002469:Cell Separation; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000473:pathology; D006402:Hematologic Diseases / Q000097:blood; D006801:Humans; D008833:Microcirculation; D008863:Microspheres; D008954:Models, Biological; D013103:Spherocytosis, Hereditary / Q000097:blood; D013154:Spleen / Q000098:blood supply* / Q000502:physiology*