Erythrocytes play a key role in human and vertebrate metabolism. Tissue O2 supply is regulated by both hemoglobin (Hb)-O2 affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenation-deoxygenation transitions of Hb may lead to re-organization of the cytoskeleton and signalling pathways activation/deactivation in an O2-dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenation-dependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg2+, 2,3-diphosphoglycerate, NO, shear stress and Ca2+, all factors accompanying the oxygenation-deoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O2 affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate.

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Erythrocyte signal transduction pathways, their oxygenation dependence and functional significance.

According to the World Health Organization the global estimate of malaria is over 200 million infections, the majority of which are caused by the most life-threatening species, Plasmodium falciparum (Report of the Steering Committees of the Scientific Working Groups on Malaria, World Health Organization, June 1983). The causative agent of the disease, the malarial parasite, requires two hosts: a blood-sucking mosquito and a blood-containing vertebrate. Commonly, infection of the vertebrate begins when an infected mosquito bites a suitable vertebrate and injects minute sporozoites into the bloodstream. Within 30 mm the introduced sporozoites leave the bloodstream and enter parenchymal cells of the liver (mammals) or endothelial cells (birds). In these sites the parasite undergoes asexual multiplication (= exo-erythrocytic schizogony) producing daughter progeny called merozoites. The exo-erythrocytic merozoites are released from the tissues into the circulation where they invade red blood cells. Within an erythrocyte the merozoite undergoes asexual multiplication (= erythrocytic schizogony) producing a substantial number of merozoites. The erythrocyte lyses, merozoites are released, and invasion of another erythrocyte may then take place. The synchronous rupture of the red cell and merozoite release is marked by the periodic fever–chill cycles so characteristic of the malarial infection. Some merozoites continue to reinvade other erythrocytes and multiply by asexual means, whereas others enter erythrocytes and differentiate into sexual stages, male or female gametocytes. When a suitable mosquito feeds on an infected vertebrate gametocytes are ingested and the sexual cycle of development is initiated. In the mosquito stomach the gametocytes transform into gametes, fertilization takes place, the resultant worm-like zygote penetrates the cells of the mosquito gut and comes to lie on the outer surface of the stomach. Here each zygote forms a cyst-like body, the oocyst, within which thousands of sporozoites are produced by asexual multiplication. When the swollen oocysts burst, sporozoites are freed and these make their way to the salivary gland. At the next blood feeding the mosquito injects the infective sporozoites and the life-cycle is completed.

Membrane structure and function of malaria parasites and the infected erythrocyte.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2878%2980470-0

Cross‐linking of red blood cell membrane proteins induced by oxidative stress in β thalassemia

There are three basic approaches to the global control of malaria: interruption of mosquito-dependent transmission of the disease through destruction of mosquito habitats and use of insecticides and larvicides; chemoprophylaxis or symptomatic treatment of the disease with drugs; and the development of a malaria vaccine. Recent resurgences in the incidence of malaria have been due partly to the emergence of insecticide and larvicide-resistant mosquitos, and drug-resistant strains of the asexual malaria parasite. As a consequence, several strategies to vaccine development are being actively pursued. In this review we will describe in detail only one approach; the identification of alterations in the surface components of malaria-infected erythrocytes which might constitute targets for host-protective (i.e., parasiticidal) immune responses. In addition to vaccine development, exploration of erythrocyte membrane changes during malaria infection is also prompted by the profound anemia accompanying this disease. The destruction of red blood cells (RBCs) during malaria infection far exceeds that expected on the basis of parasite growth alone (reviewed in Zuckerman 1966), and may reflect host elemination of uninfected RBCs due to parasite-induced antigenic alterations.

Alterations in the surface membrane of red blood cells during malaria.

A cytoplasmic requirement of red cells for invasion by malarial parasites

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2877%2980287-1

P. Chaimanee

Papers

Binding of haemoglobin to spectrin of human erythrocytes.

Phosphorylation of membrane proteins from Plasmodium berghei-infected red cells.