Significant Biochemical, Biophysical and Metabolic Diversity in Circulating Human Cord Blood Reticulocytes

Author(s):Show less -

Malleret, Benoit ^[1] ; Xu, Fenggao ^[2] ; Mohandas, Narla ^[3] ; Suwanarusk, Rossarin ^[1] ; Chu, Cindy ^[4] ; Leite, Juliana A. ^{[5, 1]} ; Low, Kayen ^[6] ; Turner, Claudia ^[4] ; Sriprawat, Kanlaya ^[4] ; Zhang, Rou ^[7] ; Bertrand, Olivier ^{[8, 9, 10]} ; Colin, Yves ^{[8, 9, 10]} ; Costa, Fabio T. M. ^[5] ; Ong, Choon Nam ^[2] ; Ng, Mah Lee ^[11] ; Lim, Chwee Teck ^{[7, 12, 13]} ; Nosten, Francois ^{[14, 15]} ; Renia, Laurent ^[1] ; Russell, Bruce ^[11]

Affiliation:Show less -

^[1] ASTAR, Biopolis, Lab Malaria Immunobiol, Singapore Immunol Network SIgN, Singapore - Singapore

^[2] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548 - Singapore

^[3] New York Blood Ctr, Red Cell Physiol Lab, New York, NY 10021 - USA

^[4] Shoklo Malaria Res Unit, Mae Sot - Thailand

^[5] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Genet Evolucao & Bioagentes, Sao Paulo - Brazil

^[6] JEOL Asia Pte Ltd, Singapore - Singapore

^[7] Natl Univ Singapore, Singapore MIT Alliance, Singapore 117548 - Singapore

^[8] Univ Paris 07, Paris - France

^[9] INSERM, UMR S Unite Mixte Rech 665, Paris - France

^[10] Inst Natl Transfus Sanguine, F-75015 Paris - France

^[11] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Natl Univ Hlth Syst, Singapore 117595 - Singapore

^[12] Natl Univ Singapore, Dept Bioengn, Singapore 117548 - Singapore

^[13] Natl Univ Singapore, Dept Mech Engn, Singapore 117548 - Singapore

^[14] Mahidol Oxford Univ, Res Unit, Bangkok - Thailand

^[15] Univ Oxford, Churchill Hosp, Ctr Trop Med, Oxford - England

• Document type: Journal article
• Source: PLoS One; v. 8, n. 10 OCT 8 2013.
• Web of Science Citations: 40

Abstract

Background: The transition from enucleated reticulocytes to mature normocytes is marked by substantial remodeling of the erythrocytic cytoplasm and membrane. Despite conspicuous changes, most studies describe the maturing reticulocyte as a homogenous erythropoietic cell type. While reticulocyte staging based on fluorescent RNA stains such as thiazole orange have been useful in a clinical setting; these `sub-vital' stains may confound delicate studies on reticulocyte biology and may preclude their use in heamoparasite invasion studies. Design and Methods: Here we use highly purified populations of reticulocytes isolated from cord blood, sorted by flow cytometry into four sequential subpopulations based on transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and CD71negative. Each of these subgroups was phenotyped in terms of their, morphology, membrane antigens, biomechanical properties and metabolomic profile. Results: Superficially CD71high and CD71medium reticulocytes share a similar gross morphology (large and multilobular) when compared to the smaller, smooth and increasingly concave reticulocytes as seen in the in the CD71low and CD71negativesamples. However, between each of the four sample sets we observe significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations. Interestingly increasing amounts of boric acid was found in the mature reticulocytes. Conclusions: Reticulocyte maturation is a dynamic and continuous process, confounding efforts to rigidly classify them. Certainly this study does not offer an alternative classification strategy; instead we used a nondestructive sampling method to examine key phenotypic changes of in reticulocytes. Our study emphasizes a need to focus greater attention on reticulocyte biology. (AU)