title: Phenylhydrazine as a partial model for beta-thalassaemia red blood cell hemodynamic properties.
abstract: beta-Thalassaemia is a congenital haemoglobinopathy, associated with red blood cells (RBC) anomalies, leading to impairment of their flow-affecting properties, namely, RBC deformability, self-aggregability, and adherence to endothelial cells (EC). Treatment of normal RBC with phenylhydrazine (PHZ) causes selective association of oxidized alpha-globin chains with the membrane skeleton, leading to reduced RBC deformability, characteristic of beta-thalassaemia. PHZ has thus been used to mimic phenotypes of beta-thalassaemia RBC. The present study was undertaken to further elucidate the suitability of PHZ-treated RBC as a model for beta-thalassemic RBC, by comparing the aggregability and adhesiveness of PHZ-treated RBC to those of RBC from thalassaemia intermedia (TI) patients, using image analysis of RBC under flow. In addition, the externalization of phosphatidylserine (PS), a mediator of RBC/EC interaction, was determined. It was found that PHZ caused enhanced RBC adhesiveness to extracellular matrix, similar to TI-RBC. Furthermore, in both conditions, the enhanced adhesiveness was mediated by PS translocated to the RBC surface. In contrast, PHZ treatment completely abolished RBC aggregability, while TI-RBC aggregability was slightly elevated. It is proposed that PHZ-treated RBC resemble beta-thalassaemia RBC in their deformability and adhesiveness, but not in their aggregability, and thus can be used as a limited model for beta-thalassaemia RBC phenotypes.
authors.affiliation: Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.forename: Alexander
authors.initials: A
authors.lastname: Koshkaryev
authors.forename: Ada
authors.initials: A
authors.lastname: Goldfarb
authors.forename: Saul
authors.initials: S
authors.lastname: Yedgar
authors.forename: Gregory
authors.initials: G
authors.lastname: Barshtein
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004903:Erythrocyte Aggregation / Q000187:drug effects; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D018056:Hemorheology / Q000187:drug effects; D006801:Humans; D008955:Models, Cardiovascular; D010659:Phenylhydrazines / Q000494:pharmacology*; D017086:beta-Thalassemia / Q000097:blood*
chemical_list: D010659:Phenylhydrazines; C030299:phenylhydrazine