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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-cell interactions are important in intravascular inflammation. Neutrophils and monocytes adhere to the vascular endothelium and release mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and reactive oxygen species. Red blood cells (RBC) from patients with malaria, sickle cell anemia, and diabetes also adhere to endothelial cells. The objectives of this investigation were to develop a bovine system of RBC adhesion to endothelial cells and to begin to investigate the mechanisms involved in the RBC adhesion. We show that 51Cr-RBC adhere to bovine pulmonary artery endothelial cells (BPAEC) after stimulation of both cell types with endotoxin (ETX; 50 micrograms/ml). RBC adhesion to BPAEC depended on the ETX concentration and the presence of divalent cations. TNF-alpha, IL-1 beta, and antioxidants (superoxide dismutase; catalase; and dimethyl sulfoxide) all induced RBC adhesion to BPAEC. Phosphatidylserine, which has been implicated in adhesion of sickle cells and aged RBC to endothelium, reduced RBC adhesion to BPAEC, whether ETX-treated or not. In conclusion, ETX, proinflammatory cytokines and, surprisingly, antioxidants increase RBC adherence to BPAEC monolayers. RBC adhesion to endothelium is decreased by phosphatidylserine.
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PMID:Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells. 877 24

Phosphatidylserine (PS) is a membrane phospholipid which in intact cells is exclusively localized in the inner leaflet of the lipid bilayer. However, once cells undergo apoptosis or oxidative stress, PS molecules are exposed on the external surface of the cells and this contributes to their adherence to macrophages or endothelial cells. PS exposure on Plasmodium falciparum-infected red cells was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS. Involvement of exposed PS in the adherence of malaria-infected red cells to endothelial cells was examined by in vitro cytoadherence assays. Infected cells exposed PS on their surface as the intracellular parasites matured to trophozoite and schizont stages. Adherence of malaria-infected cells to CD36, CD36-expressing Chinese hamster ovary cells, thrombospondin, and C32 amelanotic melanoma cells was inhibited by annexin V, whereas ICAM-1- and chondroitin sulfate A-mediated binding was not. Further, PS liposomes and glycerophosphorylserine, but not phosphatidylcholine liposomes and glycerophosphorylcholine, inhibited the binding of infected cells to CD36 and thrombospondin. In conclusion, these results demonstrate that PS exposed on the surface of malaria-infected red cells contributes, in part, to the adherence of P. falciparum-parasitized red cells to CD36 and thrombospondin.
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PMID:Cytoadherence of malaria-infected red blood cells involves exposure of phosphatidylserine. 1243 74

Glycophorin-C (GPC) is a 40 kDa glycoprotein expressed on erythrocytes and is a receptor for the malarial parasite Plasmodium falciparum to invade these cells. A link between GPC binding (ligation) and phosphatidylserine (PS) expression on erythrocytes has been suggested by its appearance on P. falciparum-infected erythrocytes. Phosphatidylserine expression has also been shown to be a marker of cellular death in a number of biological pathways including some in erythrocytes. Using Annexin V binding, we demonstrated that ligation of GPC with mouse mAb (BRIC-10) induced PS expression on normal erythrocytes. Phosphatidylserine exposure was prevented following tryptic digestion of intact erythrocytes. In addition, GPC variant phenotypes Yus (Delta exon 2) and Gerbich (Delta exon 3), which express a truncated extracellular domain, did not express PS following BRIC-10 binding, whereas PS was exposed on Ls(a) erythrocytes (duplication of exon 3). GPC ligation was also shown to result in a concomitant loss of erythrocyte viability in wild-type erythrocytes after 24 h in vitro. These results identify a potential pathway linking GPC to PS exposure on erythrocytes that may have a role in regulating red cell turnover. Further characterization of this pathway may also identify new targets for the treatment of P. falciparum malaria.
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PMID:Expression of phosphatidylserine (PS) on wild-type and Gerbich variant erythrocytes following glycophorin-C (GPC) ligation. 1580 65

Eryptosis, the suicidal death of erythrocytes, is characterised by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognised by macrophages, which engulf and degrade the affected cells. Reported triggers of eryptosis include osmotic shock, oxidative stress, energy depletion, ceramide, prostaglandin E(2), platelet activating factor, hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine, methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin, aluminium, mercury, lead and copper. Diseases associated with accelerated eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and activation of G-kinase. Most triggers of eryptosis except oxidative stress are effective without activation of caspases. Their signalling involves formation of prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows defective erythrocytes to escape hemolysis. On the other hand, excessive eryptosis favours the development of anemia. Thus, a delicate balance between proeryptotic and antieryptotic mechanisms is required to maintain an adequate number of circulating erythrocytes and yet avoid noneryptotic death of injured erythrocytes.
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PMID:Erythrocyte programmed cell death. 1872 Apr 18

Chlorpromazine has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Premature suicidal death of infected erythrocytes is in turn considered to delay development of parasitemia and thus favourably influence the clinical course of malaria. The present experiments have been performed to explore whether chlorpromazine influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of P. berghei infected mice. Phosphatidylserine was estimated from annexin V binding and cell volume from forward scatter in FACS analysis. In vitro infection of human erythrocytes increased annexin binding and decreased forward scatter, effects augmented in the presence of chlorpromazine (>or=10 microM). Chlorpromazine did not significantly alter intraerythrocytic DNA/RNA content but significantly (>or=1 microM) decreased in vitro parasitemia. In chlorpromazine treated mice erythrocytes were more rapidly cleared from circulating blood than in nontreated mice. Parasitemia in P. berghei infected mice was significantly decreased (from 50 % to 28 % of circulating erythrocytes 22 days after infection) and mouse survival significantly enhanced (from 0 % to 80 % 30 days after infection) by addition of 1 mM chlorpromazine to the drinking water from the first day of infection. In conclusion, chlorpromazine favourably influences the course of malaria, an effect at least partially due to stimulation of suicidal erythrocyte death.
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PMID:Influence of chlorpromazine on eryptosis, parasitemia and survival of Plasmodium berghe infected mice. 1876 53

Plasmodia express a sphingomyelinase, which is apparently required for their development. On the other hand, the sphingomyelinase product ceramide has previously been shown to delay parasite development. Moreover, ceramide triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Accelerated eryptosis of infected erythrocytes is considered to clear infected erythrocytes from circulating blood and, thus, to favourably influence the clinical course of malaria. The present experiments explored whether the sphingomyelinase inhibitor amitriptyline or genetic knockout of host acid sphingomyelinase influence in vitro parasite growth, eryptosis of Plasmodium falciparum-infected human erythrocytes, in vivo parasitemia and survival of P. berghei-infected mice. Phosphatidylserine exposure was determined by annexin V-binding and cell volume by forward scatter in FACS analysis. In vitro infection of human erythrocytes increased annexin- binding, an effect blunted in the presence of amitriptyline (>or=50 microM). Amitriptyline did not significantly alter intraerythrocytic parasite development but significantly (>or= 1 microM) delayed the increase in parasitemia in vitro. Most importantly, amitriptyline treatment (1 mM in drinking water) resulted in a significant delay of parasitemia and death of infected mice. However, upon infection, ceramide formation was stimulated in both, acid sphingomyelinase knockout mice (Smpd1(-/-)) and their wild type littermates (Smpd1(+/+)). Parasitemia following P. berghei infection was significantly lower in Smpd1(-/-) than in Smpd1(+/+) mice but did not significantly extend the life span of infected animals. In conclusion, mammalian and parasite sphingomyelinase contribute to ceramide formation during malaria, whereby the parasite sphingomyelinase ultimately determines the course of the infection. Amitriptyline presumably blocks both sphingomyelinases and, thus, its use might be a novel strategy to treat malaria.
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PMID:Influence of amitriptyline on eryptosis, parasitemia and survival of Plasmodium berghei-infected mice. 1908 22

Paclitaxel triggers suicidal erythrocyte death or eryptosis, characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Eryptosis of infected erythrocytes may delay development of parasitemia and thus favourably influence the course of malaria. The present study explored whether paclitaxel influences in vitro parasite growth and eryptosis of Plasmodium falciparum infected human erythrocytes and in vivo parasitemia and survival of Plasmodium berghei infected mice. Phosphatidylserine exposing erythrocytes were identified utilizing annexin V binding and erythrocyte volume was estimated from forward scatter in FACS analysis. In vitro infection of human erythrocytes with P. falciparum increased annexin binding and decreased forward scatter, effects augmented in the presence of paclitaxel (> or = 0.01 microM). Paclitaxel (> or = 0.01 microM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia. In Plasmodium berghei infected mice parasitemia was significantly decreased (from 55.8% to 28.6% of circulating erythrocytes 20 days after infection) and mouse survival significantly enhanced (from 0% to 69.23% 25 days after infection) by administration of 8.5 mg/kg.b.w. of paclitaxel intraperitoneally from the eighth day of infection. In conclusion, paclitaxel decreases parasitemia and enhances survival of P. berghei infected mice, an effect, which may be due to stimulation of eryptosis and/or a direct toxic effect on the parasite.
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PMID:Influence of paclitaxel on parasitemia and survival of Plasmodium berghei infected mice. 1925 13

The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.
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PMID:Suicide for survival--death of infected erythrocytes as a host mechanism to survive malaria. 1971 May 27

Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Amphotericin B has previously been shown to trigger suicidal erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether amphotericin B exerts a direct effect on Plasmodium falciparum and influences eryptosis of infected erythrocytes, parasitemia and host survival in murine malaria. To this end, human erythrocytes were infected in vitro with Plasmodium falciparum and mice were infected with Plasmodium berghei ANKA by in vivo intraperitoneal injection of parasitized murine erythrocytes (1x10(6)). Half of the infected mice received amphotericin B (1.5 mg/kg b.w. i.v.) from the 8(th) day of infection. Amphotericin B (> or = 1 microM) compromised the intracellular development of the parasite in human erythrocytes as evident from in vitro growth and DNA amplification assays. Amphotericin B further augmented the eryptosis of infected human erythrocytes. The administration of amphotericin B to infected mice tended to delay the increase of parasitemia and significantly delayed host death. All nontreated mice died from malaria within 27 days. In contrast, some 50% of amphotericin B-treated mice survived for more than 27 days after infection. In conclusion, amphotericin B augmented the suicidal death of infected erythrocytes and delayed the lethal course of malaria in Plasmodium berghei infected mice.
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PMID:Effect of amphotericin B on parasitemia and survival of plasmodium berghei-infected mice. 2079 19

Eryptosis, the suicidal death of erythrocytes, is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Triggers of eryptosis include anandamide. Enhanced eryptosis of infected human erythrocytes is expected to delay the development of parasitaemia during infection with Plasmodium, the parasite causing malaria. The present experiments aimed to test, whether anandamide influences eryptosis, parasite growth and/or host survival during in vitro or in vivo infection with Plasmodia. Human erythrocytes were infected in vitro with P. falciparum, and mice in vivo with P. berghei. Parasitemia was determined with Syto16. Phosphatidylserine-exposing erythrocytes were identified by analysing annexin V-binding in FACS analysis. In vitro infection of human erythrocytes was followed by a significant increase in annexin V-binding, an effect slightly enhanced by anandamide (> or = 50 microM), which significantly reduced intraerythrocytic DNA/RNA content and in vitro parasitaemia. In vivo administration of anandamide (5 mg/kg b.w. subcutaneously) blunted the parasitaemia (from 36.9% to 24.2% of circulating erythrocytes 21 days after infection) and significantly enhanced the survival of P. berghei-infected mice (from 0% to 67% 26 days after infection). The percentage of phosphatidylserine-exposing erythrocytes was significantly increased in anandamide-treated infected mice compared to non-treated infected mice. In conclusion, anandamide stimulated eryptosis of infected erythrocytes thus counteracting parasitaemia and a lethal course of the disease.
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PMID:Effect of anandamide in Plasmodium Berghei-infected mice. 2079 20


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