Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes

Abstract

The intraerythrocytic development of the malaria parasite is accompanied by distinct morphological and biochemical changes in the host cell membrane, yet little is known about development-related alterations in the transbilayer organization of membrane phospholipids in parasitized cells. This question was examined in human red cells infected with Plasmodium falciparum. Normal red cells were infected with strain FCR3 or with clonal derivatives that either produce (K+) or do not produce (K-) knobby protuberances on the infected red cells. Parasitized cells were harvested at various stages of parasite development, and the bilayer orientation of red cell membrane phospholipids was determined chemically using 2,4,6-trinitrobenzene sulphonic acid (TNBS) or enzymatically using bee venom phospholipase A2 (PLA2) and sphingomyelinase C (SMC). We found that parasite development was accompanied by distinct alterations in the red cell membrane transbilayer distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Increases in the exoplasmic membrane leaflet exposure of PE and PS were larger in the late-stage parasitized cells than in the early-stage parasitized cells. Similar results were obtained for PE membrane distribution using either chemical (TNBS) or enzymatic (PLA2 plus SMC) methods, although changes in PS distribution were observed only with TNBS. Uninfected cohort cells derived from mixed populations of infected and uninfected cells exhibited normal patterns of membrane phospholipid organization. The observed alterations in P falciparum-infected red cell membrane phospholipid distribution, which is independent of the presence or absence of knobby protuberances, might be associated with the drastic changes in cell membrane permeability and susceptibility to early hemolysis observed in the late stages of parasite development.

Enhanced Mg2+‐ATPase activity in ghosts from HS erythrocytes and in normal ghosts stripped of membrane skeletal proteins may reflect enhanced aminophospholipid translocase activity

“…The cells from the recessive HS patients exhibited low levels of spectrin, ranging from 34% to 59% of that in normal controls. In spite of this deficiency and the eventual structural defects in the membrane skeletons of others, all patients' erythrocytes showed an essentially normal phospholipid asymmetry when probed with bee venom phospholipase A2 and S. aureus sphingomyelinase C. This contrasts with earlier observations on HS erythrocytes from a patient who had approximately one-third the normal complement of spectrin and in which bee venom PLAz and TNBS detected enhanced accessibilities of both PE and PS (Schwartz et al, 1985). However, in the latter study, nothing is known about the energy status of those HS cells at the time their phospholipid topology was determined.…”

“…In erythrocytes the aminophospholipids PS and phosphatidylethanolamine (PE) are mainly (PE), or even exclusively (PS), located in the inner membrane leaflet, whereas the choline-containing phospholipids, phosphatidylcholine (PC) and sphingomyelin (SM), are enriched in the outer monolayer of the lipid bilayer (Verkleij et aJ, 1973). In a patient suffering from HS an enhanced accessibility of both PE and PS towards exogenous probes such as bee venom phospholipase A2 and trinitrobenzenesulphonic acid ("3s) has been observed (Schwartz et al, 1985). More recently, however, normal transbilayer distributions of the endogenous phospholipids, most specifically for PS.…”

Premature removal of uninfected erythrocytes during malarial infection of normal and immunodeficient mice

“…Moreover, normal asymmetrical distribution of the membrane phospholipids in uninfected erythrocytes has been shown by other workers [7,8]. The disruption of the exposure of certain phospholipids in infected erythrocytes is still a contentious point, although work by Moll et al [8] would suggest that infected erythrocytes do not show any deviation from the normal state and that observations by other groups may be a result of procedural oversights [9][10][11].…”

Temperature effects on cation transport in hereditary stomatocytosis and allied disorders

“…As pointed out in the Introduction, there are disturbances of lipid handling in some these conditions and these probably underlie the ion leak, although this is not yet clear. In cryohydrocytosis, an abnormality in the susceptibility of phosphatidylcholine to phospholipase at low temperatures, possibly reflecting abnormal 'packing' at low temperatures, has been described (Schwartz et al 1985). In poikilotherms, adaptive changes in phospholipid acyl chain composition occur with changing ambient temperature (Tiku et al 1996), reflecting the importance of lipid composition in temperature effects, and while the red cells of a homeotherm could not possibly be expected to show such adaptive reconstruction, these studies do illustrate the importance in biology of lipid acyl chain composition in the context of temperature.…”