Abstract

We study the effect of different chemical moieties on the rigidity of red blood cells (RBCs) induced by Plasmodium falciparum infection, and the bystander effect previously found. The infected cells are obtained from a culture of parasite-infected RBCs grown in the laboratory. The rigidity of RBCs is measured by looking at the Brownian fluctuations of individual cells in an optical-tweezers trap. The results point towards increased intracellular cyclic adenosine monophosphate (cAMP) levels as being responsible for the increase in rigidity.

Highlights

  • Malaria remains a global health burden[1,2], and can even result in death of infected patients

  • Conditioned media from cultured iRBCs when added to non-infected red blood cells (RBCs) render their plasma membrane more rigid implying that iRBCs secrete into the media a metabolite(s) that has both autocrine and in trans effects on RBC plasma membrane deformability; a phenomenon we termed the bystander effect[4], and have hypothesized that it corresponded to released adenosine triphosphate (ATP), or its breakdown products adenosine and inosine[6]

  • We tested that the changes in membrane deformability induced by the bystander effect are derived from the breakdown of ATP leading to an increase in intracellular cyclic adenosine monophosphate (cAMP) levels of both iRBCs and non-infected RBCs

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Summary

Introduction

Malaria remains a global health burden[1,2], and can even result in death of infected patients. This is true among children, because their immune system is not so well developed. We found a bystander effect, in which hosting and non-hosting RBCs showed the same change in properties. The results are preliminary, but suggest that the increased rigidity is caused by an increase in intracellular cAMP levels. The increase in cAMP levels being responsible for the increased rigidity is consistent with a model presented by some of us[6], where the rise in intracellular cAMP levels activates protein kinase A (PKA) to phosphorylate RBC cytoskeletal proteins

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