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: Guillaume Deplaine, Innocent Safeukui, Fakhri Jeddi, François Lacoste, Valentine Brousse, Sylvie Perrot, Sylvestre Biligui, Micheline Guillotte, Corinne Guitton, Safi Dokmak, Béatrice Aussilhou, Alain Sauvanet, Dominique Cazals Hatem, François Paye, Marc Thellier, Dominique Mazier, Geneviève Milon, Narla Mohandas, Odile Mercereau-Puijalon, Peter H David, Pierre A Buffet
• Journal: Blood (Blood) Vol. 117 Issue 8 Pg. e88-95 (Feb 24 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21163923 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Cell Separation
• Erythrocyte Deformability
• Erythrocytes (pathology)
• Hematologic Diseases (blood)
• Humans
• Microcirculation
• Microspheres
• Models, Biological
• Spherocytosis, Hereditary (blood)
• Spleen (blood supply, physiology)