In Vivo Splenic Clearance Correlates with In Vitro Deformability of Red Blood Cells from Plasmodium yoelii-Infected Mice

Abstract

Recent experimental and clinical studies suggest a crucial role of mechanical splenic filtration in the host's defense against malaria parasites. Subtle changes in red blood cell (RBC) deformability, caused by infection or drug treatment, could influence the pathophysiological outcome. However, in vitro deformability measurements have not been directly linked in vivo with the splenic clearance of RBCs. In this study, mice infected with malaria-inducing Plasmodium yoelii revealed that chloroquine treatment could lead to significant alterations to RBC deformability and increase clearance of both infected and uninfected RBCs in vivo. These results have clear implications for the mechanism of human malarial anemia, a severe pathological condition affecting malaria patients.

Large-Volume Microfluidic Cell Sorting for Biomedical Applications

“…Specifically, when compared with deformable RBCs, the stiffer RBCs isolated by the μBM device displayed higher mechanical retention in the spleen, deteriorated osmotic fragility, and higher microparticle content. These results are in agreement with previous findings (174,178,181) and support the use of single RBC deformability as a biomarker to separate good RBCs from bad. Additionally, this margination system has already been tested for higher throughput (approximately 150 mL/h) using whole blood (167), making it a good candidate for clinical applications.…”

“…Although the details of this system have not been revealed, scaling microfluidic designs for processing larger volumes is reportedly a major hurdle. The Han group (177,178) is investigating the applicability of using the μBM cell sorter to remove bad RBCs from refrigerated blood. Since the μBM device could separate deformable RBCs from their stiffer counterparts, the rationale for using the μBM device to improve blood transfusion lies in the fact that RBC aging and damage occurring during ex vivo storage coincide with a decrease in cellular deformability (179,180).…”

Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria

“…Similarly, only a minority of mature gametocytes exposed to DMSO and a majority of those exposed to calyculin were cleared. This strongly suggests that calyculin induces the clearance of mature gametocytes in vivo by inducing their mechanical retention in the spleen (39).…”

Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage

“…9 A separate work by Huang et.al also demonstrated on a malarial mice model that increased RBC stiffness associated with increased spleen mass and RBC retention. 15 Impaired deformability, therefore, may be an important biomarker for the old stored RBC subpopulation to be cleared post transfusion. 9, 15 …”