UMLS:C0024530 - FACTA Search

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

To determine splenic Fc receptor function in patients with acute Plasmodium falciparum malaria, the clearance of IgG-coated autologous 51Cr-labeled erythrocytes in 20 patients and 10 normal controls was studied. Clearance half-times were directly correlated with both the absolute parasite count (r = .635, P less than .005) and hematocrit (r = .791, P less than .001). Clearance half-times in patients varied from 1.0 to 96.3 h (median, 14.8 h) while those of controls ranged from 8.0 to 80.3 h (median, 23.1 h) (P = .10). Nine of the 20 patients had clearance half-times shorter than the lower 95% confidence limit of controls (less than 12.4 h). The clearance of IgG-coated erythrocytes was accelerated after parasites were eliminated from the circulation (P less than .05) and returned toward normal 6-8 weeks after the acute infection. Although circulating immune complexes were detectable, there was no correlation between immune complex levels and clearance half-times (P greater than .05). The failure to increase Fc receptor-mediated red cell clearance in patients with high parasitemias suggests inadequate splenic phagocytic activity in the face of considerable antigenic challenge. These findings indicate that splenic Fc receptor function may be important both in the control of infection and the development of anemia in P. falciparum malaria.
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PMID:Splenic Fc receptor function in host defense and anemia in acute Plasmodium falciparum malaria. 217 26

The squirrel monkey Saimiri sciureus is one of the World Health Organization recommended experimental models of Plasmodium falciparum blood stage infection. Anti-malaria antibodies developed by this host after a drug-controlled infection play an important part in the acquired protection against the P. falciparum blood stages. Furthermore, the use of two anti-Saimiri immunoglobulin (Ig) monoclonal antibodies (mAb) has permitted the differentiation between protective (mAb 3A2/G6) and non-protective (mAb 3E4/H8) antibodies, as shown by transfer experiments to recipient monkeys infected with blood stage parasites. In the present study we have established that protection conferred by the 3A2/G6+ protective Ig preparation is strictly associated with an in vitro opsonic activity. Such an opsonic activity is not detectable in the 3E4/H8+ non-protective Ig population. In addition, results indicate that the 3E4/H8+ non-protective Ig population competes with protective opsonic 3A2/G6+ Ig antibodies when co-incubated with parasitized red blood cells. Thus, it follows that protection can be directly correlated to the quantitative and qualitative fluctuation of the two Ig populations. When challenged with 1 x 10(8) P. falciparum-infected Saimiri red blood cells parasitemia occurred in 5 out of 12 Saimiri who were lacking detectable 3A2/G6+ opsonic antibodies in their sera. By employing antibodies against the human Fc receptor for IgG (Fc gamma R) in an in vitro phagocytic assay, we have been able to show that the principal receptor is Fc gamma RIII. Finally, we also show that in contrast to the situation in man, this receptor is present on circulating monocytes. These findings could lead to a different strategy in designing malaria vaccine candidates and also allow the possibility of predicting the outcome of immunization trials in Saimiri monkeys.
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PMID:Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus. 224 60

Culture supernatants from antigen-pulsed spleen cells of mice infected previously with either BCG or Plasmodium chabaudi were used to study macrophage activation as judged by phagocytosis of immunoglobulin G-sensitized erythrocytes and Plasmodium berghei- and P. chabaudi-infected erythrocytes. Resident peritoneal macrophages were incubated in vitro with spleen cell factor and then assayed for ingestion of immunoglobulin G-sensitized or parasitized erythrocytes. Macrophages activated with BCG-induced lymphokine bound and ingested two- to threefold more P. berghei parasitized erythrocytes than macrophages incubated with control spleen cell factor. Similarly, Plasmodium-stimulated spleen cells from mice infected with malaria produced a lymphokine(s) capable of activating macrophages for enhanced Fc receptor-mediated phagocytosis. The stimulation of phagocytosis by the lymphokine is nonspecific in nature, since phagocytosis of parasitized erythrocytes from one species of murine malaria is enhanced by the lymphokine prepared from a heterologous species. Nylon wool-nonadherent, malaria-sensitized spleen cells elaborated a lymphokine which stimulates macrophages for enhanced phagocytosis, whereas anti-0-treated spleen cells failed to produce the phagocytosis-promoting lymphokine. Consequently, this lymphokine appears to be elaborated by sensitized T lymphocytes. Interestingly, enhanced phagocytosis of opsonized trophozoites and schizonts, but not ring stage parasites of P. chabaudi, was displayed by macrophages activated with the lymphokine(s) prepared from P. chabaudi-recovered mice. Preincubation of the malaria parasitized erythrocytes with hyperimmune serum raised against the parasites greatly facilitated both binding and ingestion by the stimulated macrophages.
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PMID:Malaria-induced lymphokines: stimulation of macrophages for enhanced phagocytosis. 635 30

Immune complexes have been partially purified from the serum of Plasmodium berghei-infected mice by ultracentrifugation on 10 to 40% linear sucrose gradients, by precipitation with polyethylene glycol, and by gel filtration through Sephacryl S-300. The complexes contain gamma 1, gamma 2a, gamma 2b, and gamma 3 subclasses of mouse immunoglobulin G in differing amounts, as well as malarial antigen. Complexes isolated by all three methods inhibit Fc receptor-mediated phagocytosis by normal mouse peritoneal macrophages but do not inhibit attachment to the Fc receptor or to the C3 receptor or the ingestion of latex particles. The phagocytosis-inhibiting activity of the immune complexes can be partially removed by prior incubation with protein A-Sepharose CL-4B. Splenic macrophages, isolated from P. berghei-infected mice, may be already coated with immune complexes in vivo. Attachment of mouse erythrocytes sensitized with immunoglobulin G to these macrophages is greatly enhanced during malaria, but ingestion is not. These results suggest that immune complexes modulate the immune response to malaria by inhibiting immune phagocytosis and perhaps by interfering with other effector mechanisms. Further understanding of the influence of immune complexes and the antigens involved in these complexes may be useful in vaccine development and prophylaxis.
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PMID:Murine malaria: immune complexes inhibit Fc receptor-mediated phagocytosis. 636 90

The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression. Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls. In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals. Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression. In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls. We concluded that uncomplicated P. falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria.
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PMID:Altered expression of human monocyte Fc receptors in Plasmodium falciparum malaria. 637 11

The phagocytosis of erythrocytes may contribute to the increased susceptibility to life-threatening infections in patients with burn injury, sickle cell anemia, and malaria. The phagocytosis of immunoglobulin G-coated erythrocytes (EIgG) is followed by a transient depression of several macrophage functions including phagocytosis, respiratory burst capacity, and killing of bacteria. The present study suggests the possibility that after erythrophagocytosis hemoglobin-derived iron conspires with reactive oxygen products of the macrophage respiratory burst to cause oxidant damage to the phagocyte. Challenge of elicited peritoneal macrophages with EIgG phagocytosis was followed by an increase in lipid peroxidation as assessed by thiobarbituric acid-reactive substances (TBARS). Doses of EIgG associated with increased TBARS also caused a depression of Fc receptor-mediated phagocytosis and phorbol myristate acetate (PMA)-stimulated hydrogen peroxide production. Time course experiments demonstrated that the increase in TBARS coincided with the depression of macrophage function. There was no increase in TBARS following the phagocytosis of IgG-coated erythrocyte ghosts, suggesting that hemoglobin iron is involved in the generation of TBARS. The phagocytosis of erythrocyte ghosts did not depress macrophage function. Since complement receptor-mediated phagocytosis does not stimulate the respiratory burst, the role of the respiratory burst in causing lipid peroxidation was assessed using the phagocytosis of complement-coated erythrocytes. Phagocytic challenge with complement-coated erythrocytes caused neither an increase in TBARS nor a depression of macrophage function. However, there was an increase in TBARS when the respiratory burst was stimulated with PMA following complement receptor-mediated phagocytosis of erythrocytes. These results suggest that hemoglobin iron and phagocyte-generated oxidants collaborate to cause the depression of macrophage function following EIgG phagocytosis.
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PMID:Macrophage dysfunction following the phagocytosis of IgG-coated erythrocytes: production of lipid peroxidation products. 860 13

In Plasmodium falciparum malaria, large proportions of resident macrophages and circulating monocytes and leukocytes contain massive amounts of the malarial pigment, hemozoin. Previous studies have shown that important functions (e.g., the generation of the oxidative burst, the ability to repeat phagocytosis, and protein kinase C activity) were severely impaired in hemozoin-loaded monocytes. Expression of membrane antigens directly involved in the immune response and in the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded human monocytes was studied. Expression of major histocompatibility complex (MHC) class II after gamma interferon stimulation was blocked in hemozoin-loaded monocytes at the protein expression and gene transcription levels but was preserved in control monocytes loaded with opsonized latex beads or anti-D(Rho)-immunoglobulin G (IgG)-opsonized human erythrocytes. Expression of CD54 (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also decreased in hemozoin-loaded monocytes. Expression of MHC class I, CD16 (low-affinity Fc receptor for aggregated IgG), CD32 (low-affinity Fc receptor for aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for complement component iC3b [CR3]), CD35 (receptor for complement components C3b and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specifically affected by hemozoin loading. These results suggest that hemozoin loading may contribute to the impairment of the immune response and the derangement of antigen presentation reported in previous studies of P. falciparum malaria.
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PMID:Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes. 952 87

The mechanisms by which Abs mediate protection during blood-stage malaria infections is controversial, with some evidence pointing to the direct effect of Abs on parasite invasion and growth, while other studies suggest that Abs act in cooperation with monocytes to achieve parasite inhibition. To determine whether the effector phase of protection in vivo to the rodent parasite Plasmodium yoelii yoelii requires Fc receptor bearing cells, we passively transferred immune sera into FcR gamma-chain knockout mice. Inflammatory macrophages from these knockout mice were unable to mediate phagocytosis or Ab-dependent cell-mediated cytotoxicity (ADCC) through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Passive transfer of either P. y. yoelii hyperimmune sera or anti-GST-PYC2 sera directed to the major merozoite surface protein (MSP-1) of this parasite enabled both BALB/cByJ mice and FcR gamma-chain-deficient mice to resist lethal P. y. yoelii 17XL (Py17XL) challenge. mAb302, a protective IgG3 Ab, also passively protected both strains of mice. Most of these samples contain Ab isotypes that would not be able to protect mice if their protective effects required Ab-dependent cell-mediated cytotoxicity. These results establish that, in this infection, protection is directly mediated by Abs and does not require the participation of Fc receptors.
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PMID:Fc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model. 971 60

Plasmodium falciparum is the most lethal form of malaria and is increasing both in incidence and in its resistance to antimalarial agents. An improved understanding of the mechanisms of malarial clearance may facilitate the development of new therapeutic interventions. We postulated that the scavenger receptor CD36, an important factor in cytoadherence of P falciparum-parasitized erythrocytes (PEs), might also play a role in monocyte- and macrophage-mediated malarial clearance. Exposure of nonopsonized PEs to Fc receptor-blocked monocytes resulted in significant PE phagocytosis, accompanied by intense clustering of CD36 around the PEs. Phagocytosis was blocked 60% to 70% by monocyte pretreatment with monoclonal anti-CD36 antibodies but not by antibodies to alpha(v)beta(3), thrombospondin, intercellular adhesion molecule-1, or platelet/endothelial cell adhesion molecule-1. Antibody-induced CD36 cross-linking did result in the early increase of surface CD11b expression, but there was no increase in, or priming for, tumor necrosis factor (TNF)-alpha secretion following either CD36 cross-linking or PE phagocytosis. CD36 clustering does support intracellular signaling: Antibody-induced cross-linking initiated intracellular tyrosine phosphorylation as well as extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Both broad-spectrum tyrosine kinase inhibition (genistein) and selective ERK and p38 MAPK inhibition (PD98059 and SB203580, respectively) reduced PE uptake to almost the same extent as CD36 blockade. Thus, CD36-dependent binding and signaling appears to be crucial for the nonopsonic clearance of PEs and does not appear to contribute to the increase in TNF-alpha that is prognostic of poor outcome in clinical malaria.
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PMID:Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. 1105 8

It has been shown that administration of TNF-alpha causes an increase of survival of plasmodium-infected mice. However, this anti-parasitic effect cannot be reproduced in vitro upon direct incubation of the cytokine with the parasite. This suggests that TNF-alpha may act through modulation of some plasmodicidal mechanism not yet clarified. We evaluated the effect of exogenous TNF-alpha on the phagocytosis of Plasmodium falciparum-infected erythrocytes by monocytes and its influence on the ability of monocytes and lymphocytes to inhibit parasite growth. The capacity of endogenous TNF-alpha to influence the ability of monocytes to inhibit the parasite was also verified. We found that addition of 33 ng TNF-alpha/mL to cultures of human monocytes and P. falciparum-infected erythrocytes increased the phagocytic index from 3.8 to 7.8 in the presence of serum containing P. falciparum antibody. TNF-alpha increased the capacity of monocyte plus lymphocyte to inhibit parasite growth by about 3 times at 0.5 and 5 ng/mL. Sera from severely ill P. falciparum-infected individuals inhibited the parasite growth, but addition of anti-TNF-alpha antibody was unable to modify this inhibition. These data show that TNF-alpha can increase the phagocytic capacity. This was probably due to an increased expression of Fc receptors on monocytes or to the modulation of Fc receptor signaling pathways by signals originating from the binding of TNF-alpha to its receptors. TNF-alpha also acted on lymphocytes plus monocytes by increasing the inhibition of P. falciparum by a mechanism not related to phagocytosis. These findings suggest that TNF-alpha has a pleiotropic anti-malaria effect and that this protective effect depends on the interplay of different factors, such as monocytes/macrophages, lymphocytes, and antibodies, in addition to other cells and molecules.
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PMID:Influence of tumor necrosis factor-alpha on the ability of monocytes and lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro. 1133 39

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