Erythrocyte adhesion is modified by alterations in cellular tonicity and volume.
We tested the hypothesis that dehydration-induced alterations in red blood cell (RBC) membrane organisation or composition contribute to sickle cell adhesion in sickle cell disease (SCD). To examine the role of RBC hydration in adhesion to the subendothelial matrix protein thrombospondin-1 (TSP), normal and sickle RBCs were incubated in buffers of varying tonicity and tested for adhesion to immobilised TSP under flow conditions. Sickle RBCs exhibited a decrease in TSP binding with increasing cell hydration (P<0.005), suggesting that cellular dehydration may contribute to TSP adhesion. Consistent with this hypothesis, normal RBCs showed an increase in TSP adhesion with increasing dehydration (P<0.01). Furthermore, increased TSP adhesion of normal RBCs could also be induced by isotonic dehydration using nystatin-sucrose buffers. Finally, TSP adhesion of both sickle RBCs and dehydrated normal RBCs was inhibited by the anionic polysaccharides, chondroitin sulphate A and high molecular weight dextran sulphate, but not by competitors of CD47-, band 3-, or RBC phosphatidylserine-mediated adhesion. More importantly, we found increased adhesion of nystatin-sucrose dehydrated normal mouse RBCs to kidney capillaries following re-infusion in vivo. In summary, these findings demonstrate that changes in hydration can significantly impact adhesion, causing normal erythrocytes to display adhesive properties similar to those of sickle cells and vice versa.
Wandersee
Nancy J
NJ
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. nancy.wandersee@bcw.edu
Punzalan
Rowena C
RC
Rettig
Michael P
MP
Kennedy
Michael D
MD
Pajewski
Nicholas M
NM
Sabina
Richard L
RL
Paul Scott
J
J
Low
Philip S
PS
Hillery
Cheryl A
CA
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood*; D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003681:Dehydration; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D004913:Erythrocytes, Abnormal / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007668:Kidney / Q000098:blood supply; D051379:Mice; D009761:Nystatin / Q000494:pharmacology; D009995:Osmosis; D010718:Phosphatidylserines / Q000097:blood; D013395:Sucrose / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism*
D010718:Phosphatidylserines; D019700:Thrombospondin 1; D009761:Nystatin; D013395:Sucrose