Effects of a single sickling event on the mechanical fragility of sickle cell trait erythrocytes
Tennille D Presley, Andreas S Perlegas, Lauren E Bain, Samir K Ballas, James S Nichols, Hernan Sabio, Mark T Gladwin, Gregory J Kato, Daniel B Kim-Shapiro, Tennille D Presley, Andreas S Perlegas, Lauren E Bain, Samir K Ballas, James S Nichols, Hernan Sabio, Mark T Gladwin, Gregory J Kato, Daniel B Kim-Shapiro
Abstract
Hemolysis contributes to the pathology associated with sickle cell disease. However, the mechanism of hemolysis or relative contribution of sickling due to hemoglobin (Hb) polymerization vs. oxidative damage remains unknown. Earlier studies aimed at deciphering the relative importance of these two mechanisms have been complicated by the fact that sickle red cells (SS) have already been affected by multiple rounds of sickling and oxidative damage before they are collected. In our study, we examine the mechanical fragility of sickle cell trait cells, which do not sickle in vivo, but can be made to do so in vitro. Thus, our novel approach explores the effects of sickle Hb polymerization on cells that have never been sickled before. We find that the mechanical fragility of these cells increases dramatically after a single sickling event, suggesting that a substantial amount of hemolysis in vivo probably occurs in polymer-containing cells.
Conflict of interest statement
Declaration of Interest
Drs. Gladwin and Kim-Shapiro are listed as co-inventors of a provisional patent application entitled “Methods for treatment of hemolysis”.
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Source: PubMed