Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis. Blood 2004 Jan 15;103(2):710-6
Date
08/30/2003Pubmed ID
12947004DOI
10.1182/blood-2003-02-0492Scopus ID
2-s2.0-0942276836 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
Mice with disruptions of the red blood cell (RBC) cytoskeleton provide severe hemolytic anemia models in which to study multiorgan thrombosis and infarction. The incidence of cerebral infarction ranges from 70% to 100% in mice with alpha-spectrin deficiency. To determine whether mutant RBCs abnormally bind adhesive vascular components, we measured adhesion of mouse and human RBCs to immobilized human thrombospondin (TSP) and laminin (LM) under controlled flow conditions. Mutant RBCs had at least 10-fold higher adhesion to TSP compared with normal RBCs (P <.006). Mutant relative to unaffected RBC adhesion to LM was significantly (P <.01) increased as well. Treatment of RBCs with the anionic polysaccharide dextran sulfate inhibited mutant RBC adhesion to TSP (P <.001). Treatment of RBCs with antibodies to CD47 or the CD47-binding TSP peptide 4N1K did not inhibit TSP adhesion of RBCs. Previously, we have shown that infarcts in alpha-spectrin-deficient sph/sph mice become histologically evident beginning at 6 weeks of age. TSP adhesion of RBCs from 3- to 4- and 6- to 8-week-old sph/sph mice was significantly higher than RBCs from adult mice (> 12 weeks old; P <.005). While the mechanism of infarction in these mice is unknown, we speculate that changes in RBC adhesive characteristics contribute to this pathology.
Author List
Wandersee NJ, Olson SC, Holzhauer SL, Hoffmann RG, Barker JE, Hillery CAMESH terms used to index this publication - Major topics in bold
AnimalsCell Adhesion
Elliptocytosis, Hereditary
Erythrocytes
Humans
Laminin
Mice
Spherocytosis, Hereditary
Thrombospondins
