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

Cerebral malaria is a fatal complication of infection by Plasmodium falciparum in man. The neurological symptoms that characterize this form of malarial disease are accompanied by the adhesion of infected erythrocytes to the vasculature of the brain. To study this phenomenon in vivo, an acute phase severe combined immunodeficiency (SCID) mouse model was developed in which sequestration of P. falciparum-infected human erythrocytes took place. During acute cerebral malaria in humans, the expression of intercellular adhesion molecule-1 (ICAM-1) is induced in vascular endothelium by inflammatory reactions. Acute phase ICAM-1 expression can also be obtained in SCID mice. The endothelium of the midbrain region was the most responsive to such inflammatory stimulus. It is noteworthy that the reticular formation in the midbrain controls the level of consciousness, and loss of consciousness is a symptom of cerebral malaria. We found that infected human erythrocytes were retained 24 times more than normal erythrocytes in ICAM-1-positive mouse brain. Sequestration to the brain was reduced by anti-ICAM-1 antibodies. These in vivo results were confirmed by the binding of P. falciparum-infected erythrocytes to the ICAM-1-positive endothelium in tissue sections of mouse brain. We conclude that the SCID mouse serves as a versatile in vivo model that allows the study of P. falciparum-infected erythrocyte adhesion as it occurs in human cerebral malaria. Upregulation of ICAM-1 expression in the region of the midbrain correlates with increased retention of malaria-infected erythrocytes and with the symptoms of cerebral malaria.
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PMID:In vivo sequestration of Plasmodium falciparum-infected human erythrocytes: a severe combined immunodeficiency mouse model for cerebral malaria. 765 Apr 76

Cytoadherence to HB3 and FC27 strains of Plasmodium falciparum-parasitized red blood cells (PRBC) was studied under shear conditions to elucidate the pathways of adherence to microvascular endothelial cells (MEC). HB3 PRBC bound exclusively to MEC CD36 and intercellular adhesion molecule-1 (ICAM-1) receptors. FC27 PRBC bound to CD36 and another unidentified pathway but not to ICAM-1. Down-regulation of CD36 and ICAM-1 expression by phorbol 12,13-dibutyrate abolished HB3 PRBC adherence. Selective up-regulation of CD36 with interferon-gamma (IFN-gamma) increased PRBC adherence. Conversely, selective up-regulation of ICAM-1 with tumor necrosis factor did not elevate cytoadherence. These data have defined the relative contributions of both CD36 and ICAM-1 to PRBC binding to MEC and have provided evidence for the presence of a novel adhesion mechanism. Furthermore, in addition to antibody blocking of cell adhesion molecules, anti-IFN-gamma antibody therapy or pharmacologic manipulation of endothelial cell receptor expression may reduce PRBC sequestration and ameliorate the events associated with human cerebral malaria.
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PMID:Cytoadherence of Plasmodium falciparum-infected erythrocytes to microvascular endothelium is regulatable by cytokines and phorbol ester. 768 61

Canine intercellular adhesion molecule-1 (ICAM-1) plays a primary role in the adherence of canine neutrophils to endothelial cells and in the cytotoxicity of canine neutrophils for adult cardiac myocytes. We have cloned the canine ICAM-1 gene and have analyzed the conservation of ICAM-1 amino acid (aa) sequences in man, chimpanzee, mouse, rat and dog. Canine ICAM-1 displays 61% identity with human ICAM-1. Cys residues critical to the immunoglobulin (Ig) fold structure and four sites of N-linked glycosylation are absolutely conserved in ICAM-1 from all species. Residues in the cytoplasmic tail associated with cytoskeletal alpha-actinin binding are highly conserved, supporting the hypothesis that intracellular attachment is indeed important for ICAM-1 function. Residues critical for human ICAM-1 binding to the beta 2-integrin leukocyte-function-associated antigen 1 (LFA-1) are highly conserved between all species, whereas those residues demonstrated to play an important role in interaction of human ICAM-1 with macrophage activation complex 1 (Mac-1) are not highly conserved. Residues critical for ICAM-1 binding to rhinovirus and malaria-infected red blood cells (IRBC) are not highly conserved.
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PMID:Cloning and comparative sequence analysis of the gene encoding canine intercellular adhesion molecule-1 (ICAM-1). 775 71

Severe Plasmodium falciparum malaria is characterized by multiple organ involvement due to sequestration of infected erythrocytes in small vessels. Endothelial cell adhesion molecules play an important role in this interaction. During the course of a severe cerebral P. falciparum malaria infection we found very markedly elevated levels of the soluble adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1, with a maximum increase of nine, seven, and eight times, respectively. These very high levels of soluble adhesion molecules point to an endothelial cell injury as an additional cause to physiological release or shedding due to receptor interactions. Soluble thrombomodulin (sTM) levels showed an extremely marked elevation up to 332 ng/ml (up to 13 times the normal value) as well. Malaria patients without severe organ involvement/cerebral manifestation showed only a mild elevation of sTM levels. TM is a parameter independent of the immunological system. It is regarded as a marker of vasculitis and endothelial cell destruction. Therefore, markedly elevated sTM levels document a substantial endothelial cell injury in severe malarial infection and may be of diagnostic and prognostic importance.
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PMID:Serum levels of adhesion molecules and thrombomodulin as indicators of vascular injury in severe Plasmodium falciparum malaria. 781 16

Erythrocytes infected with mature stages of Plasmodium falciparum malaria adhere to vascular endothelial cells in postcapillary venules of several organs. In some patients, infected cells also form rosettes with uninfected erythrocytes. The special pathology of acute cerebral malaria appears to result from excessive adherence of infected cells in cerebral vessels coupled with occlusion of cerebral blood flow in microvessels by infected cell rosettes. Several endothelial cell proteins have been identified as potential receptors for infected erythrocyte adherence to vascular endothelium, including thrombospondin, CD36, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). The receptor on infected erythrocytes that mediates adhesion to endothelial cells has been identified as a very large malarial protein on infected cells called PfEMP1. PfEMP1 has been shown to bind to CD36 and thrombospondin in vitro. Antibody-mediated blockade or reversal of infected erythrocyte adherence to vascular endothelium is postulated not only to decrease the pathology of blood-stage malaria, but also to lead to infected cell destruction and clearance, especially in the spleen. PfEMP1 is therefore a prime candidate malarial protein for inclusion in a multicomponent asexual malaria vaccine.
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PMID:Malaria, the red cell, and the endothelium. 819 84

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.
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PMID:Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. 822 94

Intercellular adhesion molecule-1 and E-selectin levels were increased in the plasma of 60 falciparum malaria patients and were not related to levels of tumor necrosis factor alpha, interleukin 10, or interleukin 1 alpha. Soluble E-selectin was correlated to disease; its level in plasma was related to levels of both tumor necrosis factor soluble receptors and biological markers of disease severity and returned to baseline after parasite clearance faster than that of soluble intercellular adhesion molecule-1.
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PMID:Soluble intercellular adhesion molecule-1 and E-selectin levels in plasma of falciparum malaria patients and their lack of correlation with levels of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), and IL-10. 855 30

We have recently shown that some squirrel monkeys (Saimiri sciureus) develop cerebral malaria when experimentally infected with asexual blood stage forms of different Plasmodium falciparum isolates. Since cerebral malaria is neither an inconsistent nor predictable event, several clones of endothelial cells isolated from the squirrel monkey brain microvasculature have been developed. Infected red blood cell (IRBC) adherence involved the knobs and direct membrane interactions through pseudopodes and microvilli on the Saimiri brain endothelial cell (SBEC) surface, similar to that observed with both brain microvascular endothelial cells from a patient who died of cerebral malaria and the rhesus monkey/P. coatneyi cerebral malaria model. The involvement of pseudopodes and microvilli increase the endothelial cell surface for the attachment of IRBCs; however, they are already present before the SBECs are exposed to IRBCs. With some SBEC phenotypes, embedding of IRBCs into the cytoplasma membrane of the endothelial cell was observed, resulting in an extremely close apposition of both SBEC and IRBC membranes during the adherence process. Once IRBCs are adherent, particularly for the embedding type, heterocellular communication-like structures between the cells become apparent. The upregulation of CD36 and intercellular adhesion molecule-1 by soluble recombinant (sr)-tumor necrosis factor-alpha or sr-interferon-gamma did not modify the IRBC interactions with SBECs at the ultrastructural level. The study shows further that the observed differences of IRBC adherence are due to unidentified phenotypic differences of SBECs rather than to a parasite isolate or particular endothelial cell receptor-associated phenomenon. Exploring P. falciparum IRBC cytoadherence in the squirrel monkey using a homologous physiologic target cell model in vitro should be useful for the evaluation of vaccine strategies and drugs to prevent human cerebral malaria.
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PMID:Ultrastructural aspects of Plasmodium falciparum-infected erythrocyte adherence to endothelial cells of Saimiri brain microvasculature. 861 43

Soluble intercellular adhesion molecule-1 (sICAM-1) level was measured in sera from 41 patients with Schistosoma mansoni schistosomiasis and compared with the sICAM-1 level in 41 healthy subjects. A significant increase in serum sICAM-1 was observed in patients with schistosomiasis compared with control subjects. As they were inhabitants of the French Antilles, the patients were, however, not settled in a malaria endemic zone, allowing this cause of sICAM-1 enhancement to be eliminated. No correlation was found between the level of sICAM-1 and the schistosomiasis serological titre. Such results favour the hypothesis of an activation of vascular endothelial cells due to egg deposition.
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PMID:Endothelium activation related increase of soluble intercellular adhesion molecule-1 in human schistosomiasis. Lack of correlation with serology. 881 68

In the past, several cell lines have been used as in vitro models for studying cytoadherence, which refers to the specific binding of Plasmodium falciparum-parasitized red blood cells (PRBC) to host endothelium of microvessels. These models include: (a) human cells, including human umbilical vein endothelial cells (HUVEC), C32 amelanotic melanoma cells and monocytes; (b) non-human cells transfected with human genes, including COS and CHO cells; and (c) purified candidate receptor molecules. However, endothelial cells from malaria target organs are rarely investigated. In this study, we describe the efficient isolation and characterization of human lung endothelial cells (HLEC). This is the first in vitro study of P. falciparum PRBC cytoadherence to human lung endothelium, one of the target organs during severe malaria. The endothelial nature of the HLEC lines was confirmed by the presence of the von Willebrand factor, anti-human platelet endothelial adhesion molecule-1 and E-selectin antigens as specific endothelial markers. After exposure of HLEC to human cytokines, FACScan analysis indicated the coexpression of PRBC receptors CD36, intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1). The laboratory-adapted P. falciparum strains adhered specifically in vitro to these HLEC. The binding of PRBC could be inhibited with variable efficiency by various monoclonal antibodies (anti-CD36 > anti-ICAM-1 > anti-VCAM-1 > anti-E-selectin). Target organ specific cell lines such as HLEC expressing a variety of potential P. falciparum PRBC cytoadherence receptors may provide in vitro systems for studying the pathophysiology of severe malaria and identifying new therapeutic agents designed to directly block adhesive events involved in severe malaria.
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PMID:Primary culture of human lung microvessel endothelial cells: a useful in vitro model for studying Plasmodium falciparum-infected erythrocyte cytoadherence. 881 44


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