Submitted February 13, 2003
Accepted August 27, 2003
Increased erythrocyte adhesion in mice and humans with hereditary spherocytosis and hereditary elliptocytosis
Nancy J Wandersee*, Scott C Olson, Sandra L Holzhauer, Raymond G Hoffmann, Jane E Barker, and Cheryl A Hillery
The Jackson Laboratory, Bar Harbor, ME, USA; Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA
* Corresponding author; email: njwandersee{at}bcsew.edu.
Mice with disruptions of the red blood cell (RBC) cytoskeleton provide severe hemolytic anemia models in which to study multi-organ thrombosis and infarction. The incidence of cerebral infarction ranges from 70% to 100% in mice with 
-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 
10-fold higher adhesion to TSP compared to normal RBCs (p<0.006). Mutant relative to unaffected RBC adhesion to LM was significantly (p<0.01) increased as well. Treatment of RBCs with the anionic polysaccharide dextran sulfate inhibited mutant RBC adhesion to TSP (p<0.001). 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 -spectrin deficient sph/sph mice become histologically evident beginning at 6 wks of age. TSP adhesion of RBCs from 3-4 and 6-8 wk old sph/sph mice was significantly higher than RBCs from adult mice (>12 wk old; p<0.005). While the mechanism of infarction in these mice is unknown, we speculate that changes in RBC adhesive characteristics contribute to this pathology.
