Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of synthetic malaria pigment (beta-haematin, BH) on the expression of the intercellular adhesion molecule 1 (ICAM-1) and platelet endothelial cell adhesion molecule 1 (PECAM-1) and the production of interleukin-6 (IL-6) by human microvascular endothelial cells were measured using flow cytometry analysis and immunoenzymatic assay. BH alone did not affect basal levels of ICAM-1, PECAM-1 or IL-6. When added to cell cultures before or with, but not after, lipopolysaccharide or tumour necrosis factor alpha, BH at 1-100 micrograms/mL induced a dose-dependent inhibition of ICAM-1 and PECAM-1 expression and IL-6 production. Cell viability and human leucocyte antigen A,B,C expression remained unaffected. Similar, though more variable, results were obtained using human umbilical vein endothelial cells. These results suggested that accumulation of pigment within endothelial cells following repeated malaria infection reduces local inflammation and parasite sequestration through inhibition of either cytokine production or parasitized erythrocyte receptors on endothelial cells.
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PMID:The effect of synthetic malaria pigment (beta-haematin) on adhesion molecule expression and interleukin-6 production by human endothelial cells. 969 53

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH(2)-terminal head structure (Duffy binding-like domain 1 [DBL1alpha]-cysteine-rich interdomain region [CIDR1alpha]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate-like glucosaminoglycan, and CD36. DBL2delta was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.
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PMID:The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors. 1088 May 21

The sequestration of Plasmodium falciparum-infected erythrocytes (pRBC) away from the peripheral circulation is a property of all field isolates. Here we have examined the pRBC of 111 fresh clinical isolates from children with malaria for a number of adhesive features in order to study their possible coexpression and association with severity of disease. A large number of adhesion assays were performed studying rosetting, giant rosetting, and binding to CD36, intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, thrombospondin, heparin, blood group A, and immunoglobulins. Suspension assays were performed at the actual parasitemia of the isolate, while all the static adhesion assays were carried out at an equal adjusted parasitemia. The ability to bind to multiple receptors, as well as the ability to form rosettes and giant rosettes, was found to be more frequent among isolates from children with severe versus mild malaria (P = 0.0015). Rosettes and giant rosettes were more frequent for children with severe malaria, and the cell aggregates were larger and tighter, than for those with mild disease (P = 0.0023). Binding of immunoglobulins (97% of isolates) and of heparin (81% of isolates) to infected erythrocytes was common, and binding to heparin and blood group A was associated with severity of disease (P = 0.011 and P = 0.031, respectively). These results support the idea that isolates that bind to multiple receptors are involved in the causation of severe malaria and that several receptor-ligand interactions work synergistically in bringing about severe disease.
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PMID:Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. 1150 Apr 63

Platelet-endothelial cell adhesion molecule 1 (PECAM-1/CD31) has been identified as an endothelial cell receptor of Plasmodium falciparum-infected erythrocytes. The significance of adhesion of infected erythrocytes to this receptor in malaria infection has not been determined. We have therefore studied the association of the functional mutation CTG-->GTG (Leu-->Val) in codon 125 of the Cd31 gene with severe disease in 2 case-control studies of malaria in Madang Hospital, Papua New Guinea, and in Kilifi District Hospital, Kenya. We analyzed data from 442 cases and controls from Papua New Guinea and data from 396 cases and controls from Kenya. The codon 125 polymorphism was not associated with severe malaria in either study. We conclude that the presence of CTG-->GTG (Leu-->Val) substitution in codon 125 in CD31 is not associated with protection from severe malaria, and we suggest that selective forces other than malaria may maintain this high-frequency polymorphism.
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PMID:Short report: codon 125 polymorphism of CD31 and susceptibility to malaria. 1179 67

Intercellular adhesion molecule 1 (ICAM-1) is an endothelial cell adhesion molecule implicated in cerebral malaria. We investigated whether fibrinogen affects Plasmodium falciparum binding to ICAM-1, as the ICAM-1 binding sites of P. falciparum and fibrinogen overlap. We show that fibrinogen dramatically reduces P. falciparum adhesion to ICAM-1 under flow conditions.
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PMID:Fibrinogen binding to intercellular adhesion molecule 1: implications for Plasmodium falciparum adhesion. 1206 44

It is proposed that the surface ligands of Plasmodium falciparum infected HbAS erythrocytes, not like infected HbAA erythrocytes, are altered due to the sickling that soon takes place once a HbAS erythrocyte gets infected with P. falciparum parasite. This alteration modulates cytoadherence and/or binding of the sickled erythrocytes to the peripheral blood mononuclear cells (PBMCs). Both cytoadherence and binding to PBMCs are responsible for the pathogenesis of malaria. Therefore, subjects of the HbAS genotype experience mild symptoms of malaria. The hypothesis could be tested in vitro by comparing the binding of P. falciparum infected HbAS and HbAA erythrocytes to platelet-endothelial cell adhesion molecule-1 (CD31) and by comparing the levels of tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) following in vitro stimulation of PBMCs by HbAS and HbAA infected erythrocytes.
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PMID:Protection against severe clinical manifestations of Plasmodium falciparum malaria among sickle cell trait subjects is due to modification of the release of cytokines and/or cytoadherence of infected erythrocytes to the host vascular beds. 1269 25

Peroxisome proliferator-activated receptor gamma-retinoid X receptor (PPARgamma-RXR) agonists had minimal effects on the surface levels of CD36, intercellular cell adhesion molecule-1, or platelet-endothelial cell adhesion molecule-1 and had no effect on the cytoadherence of infected erythrocytes to either human umbilical vein endothelial cells or human microvascular endothelial cells or on malaria-induced interleukin-6 secretion from these cells. PPARgamma-RXR agonists do not significantly modify malaria-infected erythrocyte-endothelial cell interactions in vitro.
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PMID:Peroxisome proliferator-activated receptor gamma and retinoid X receptor agonists have minimal effects on the interaction of endothelial cells with Plasmodium falciparum-infected erythrocytes. 1566 66

We investigated associations between markers of damage of vascular endothelial cells (MDVECs) and plasma cytokine levels, hemoglobin level and temperature in individuals with acute uncomplicated malaria, as well as healthy controls, using enzyme linked immunosorbent assay (ELISA) for the presence of soluble endothelial cell adhesion molecule-1 (sE-selectin), circulating granule membrane protein-140 (sP-selectin), circulating thrombomodulin (TM), circulating von Willebrand factor (VWf), interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Significant differences were observed between falciparum malaria patients and the healthy people in term of levels of both sE-selectin and TM. The serum levels of sP-selectin and VWf were comparable between the two groups. The levels of both sE-Selectin and TM correlated positively with temperature, levels of IFN-gamma and levels of TNF-alpha; and negatively with hemoglobin levels. Trends of positive correlations were observed between level of sP-selectin or VWf and temperature. Furthermore, sE-selectin levels correlated with vomiting. These data suggest that sE-selectin and TM might be useful markers of endothelium activation in in vivo studies. Moreover, our results highlight the use of both sE-selctin and TM as markers of anemia.
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PMID:Markers of vascular endothelial cell damage and P. falciparum malaria: association between levels of both sE-selectin and thrombomodulin, and cytokines, hemoglobin and clinical presentation. 1877 3

Platelet/endothelial cell adhesion molecule-1 (PECAM1/CD31), a receptor recognized by P. falciparum-infected red blood cells (iRBCs), on the vascular endothelium has been implicated in mediating cytoadherence in patients with P. falciparum malaria. To examine associations of PECAM1 polymorphisms with cerebral malaria, 11 tag single nucleotide polymorphisms (SNPs) of PECAM1 were analysed for 312 Thai patients with P. falciparum malaria (109 with cerebral malaria and 203 with mild malaria). The rs1122800-C allele was significantly associated with protection from cerebral malaria (P = 0.017), and the rs9912957-A significantly increased the risk for cerebral malaria (P = 0.0065) in malaria patients. Fine-scale mapping using genotyped and imputed SNPs and linkage disequilibrium (LD) analysis revealed that rs1122800 and rs9912957 were located in two distinct LD blocks and were independently associated with cerebral malaria. The rs1122800-C allele was significantly associated with lower expression level of PECAM1 in EBV-transformed lymphoblastoid cell lines (P = 0.045). The present results suggest that PECAM1-mediated cytoadherence of iRBCs to brain endothelium plays a crucial role in the pathogenesis of cerebral malaria.
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PMID:Association of PECAM1/CD31 polymorphisms with cerebral malaria. 2733 27