A Soluble Mannose Receptor Immunoadhesin Enhances Phagocytosis of <i>Pneumocystis carinii</i> by Human Polymorphonuclear Leukocytes <i>In Vitro</i>

Stehle, S E; Rogers, Rick A.; Harmsen, Allen G.; Ezekowitz, R. A. B.

doi:10.1046/j.1365-3083.2000.00755.x

Cited by 19 publications

(10 citation statements)

References 32 publications

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“…Crystal structures of Py in complex with oligosaccharide analogs of GD1a and GT1b have illuminated the mode of binding. The disaccharide sequence N-acetylneuraminic acid (NeuAc) ␣2,3 linked to galactose (Gal), which is common to GD1a and GT1b, binds to a shallow pocket in the exposed surface of VP1 (61,62). It has been shown that the ganglioside GM1 is required for both attachment and infectivity of SV40 (68), but the structural basis for this binding and specificity remain to be clarified.…”

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confidence: 99%

N -Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

Campanero-Rhodes

Smith

Chai

et al. 2007

J Virol

151

131

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Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.

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confidence: 99%

N -Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

Campanero-Rhodes

Smith

Chai

et al. 2007

J Virol

151

131

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“…Alveolar macrophages are thought to interact with Pneumocystis organisms through the macrophage mannose receptor or the ␤-glucan receptor (30). It has been shown that a recombinant macrophage mannose receptor which consists of the ectodomain of the macrophage mannose receptor and the Fc portion of human immunoglobulin G1 binds to Pneumocystis organisms and causes an increase in phagocytosis of the organisms by macrophages (47). However, the interaction of Pneumocystis organisms with the macrophage mannose receptor does not stimulate the release of tumor necrosis factor alpha (30).…”

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confidence: 99%

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

et al. 2004

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Alveolar macrophages from Pneumocystis carinii-infected rats are defective in phagocytosis. To investigate whether this defect is due to a certain factor present in P. carinii-infected lungs, alveolar macrophages from uninfected rats were incubated with bronchoalveolar lavage (BAL) fluid samples from P. carinii-infected rats. Alveolar macrophages treated with these BAL fluid samples became defective in phagocytosis but remained normal when treated with BAL fluid samples from noninfected or Toxoplasma gondii-infected rats. The suppressive activity of the BAL fluid samples from P. carinii-infected rats on phagocytosis was retained when the BAL fluid samples were passed through a filter with a pore size of 0.45 m but was lost when the BAL fluid samples were digested with proteases such as trypsin, pepsin, papain, or endopeptidase Gly-C. Lipid fractions of these BAL fluid samples had no suppressive activity on phagocytosis. The suppressive activity of these BAL fluid samples was also lost when they were incubated with concanavalin A-agarose beads, suggesting that the inhibitor is a glycoprotein. The inhibitor was estimated to be larger than 100,000 Da by exclusion filtration. After binding to the concanavalin A-agarose beads, the inhibitor in BAL fluid samples and P. carinii lysate could be eluted with 200 mM methylmannose. Treatment of both the crude BAL fluid samples and P. carinii lysate and the 200 mM methylmannose eluate with antibody against the major surface glycoprotein of P. carinii eliminated their suppressive activity. These results suggest that the factor capable of suppressing the phagocytic activity of alveolar macrophages is P. carinii major surface glycoprotein or one or more of its derivatives.An important function of alveolar macrophages is to clear foreign particles and infectious agents from the lung. Their role in the defense against Pneumocystis carinii infection is demonstrated by the observation that transtracheally inoculated P. carinii organisms are not cleared in alveolar macrophage-depleted rats (31). Administration of granulocyte-macrophage colony-stimulating factor, which activates alveolar macrophages (40), decreases the severity of P. carinii pneumonia (34). This finding also indicates the importance of alveolar macrophages in the clearance of Pneumocystis organisms.The alveoli are constantly exposed to foreign material and microorganisms. The alveolar macrophage maintains a low level of activation to engulf and destroy these materials while inhibiting an overly reactive inflammatory reaction to foreign objects encountered. To accomplish this, alveolar macrophages inhibit antigen presentation by dendritic cells (20), limit the expansion of lymphocyte populations (38), and restrict pulmonary lymphocyte functions (19). When activated, alveolar macrophages become proinflammatory and produce interleukin-8, which attracts neutrophils and lymphocytes by chemotaxis, as well as interleukin-1␤, tumor necrosis factor alpha, interleukin-6, and granulocyte-macrophage colony-stimulating factor, wh...

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“…This activation is enhanced by vitronectin or fibronectin, which accumulates in the lung during Pneumocystis infection (29). Alveolar macrophages are thought to interact with Pneumocystis organisms through the macrophage mannose receptor or the ␤-glucan receptor (20,37).…”

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Effect of Transcription Factor GATA-2 on Phagocytic Activity of Alveolar Macrophages fromPneumocystis carinii-Infected Hosts

et al. 2003

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Experiments were performed to determine whether this defect is specific for P. carinii organisms. The results showed that these macrophages were unable to phagocytose both P. carinii organisms and fluorescein isothiocyanate (FITC)-conjugated latex beads, indicating that alveolar macrophages from P. carinii-infected hosts have a general defect in phagocytosis. To determine whether this defect correlates with the recently discovered down-regulation of the GATA-2 transcription factor gene during P. carinii infection, alveolar macrophages from dexamethasone-suppressed or healthy rats were treated with anti-GATA-2 oligonucleotides and then assayed for phagocytosis. Aliquots of the alveolar macrophages were also treated with the sense oligonucleotides as the control. Cells treated with the antisense oligonucleotides were found to have a 46% reduction in phagocytosis of P. carinii organisms and a 65% reduction in phagocytosis of FITC-latex beads compared to those treated with the sense oligonucleotides. To determine whether the defect in phagocytosis in alveolar macrophages from P. carinii-infected hosts can be corrected by overexpression of GATA-2, a plasmid containing the rat GATA-2 gene in the sense orientation driven by the cytomegalovirus (CMV) promoter was introduced into alveolar macrophages from P. carinii-infected rats. Aliquots of the same cells transfected with a plasmid containing GATA-2 in the antisense orientation relative to the CMV promoter served as the control. Alveolar macrophages treated with the sense GATA-2 expression construct were found to increase their phagocytic activity by 66% in phagocytosis of P. carinii organisms and by 280% in phagocytosis of FITC-latex beads compared to those that received the antisense GATA-2 construct. The results of this study indicate that GATA-2 plays an important role in the regulation of phagocytosis in alveolar macrophages during P. carinii infection.

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A Soluble Mannose Receptor Immunoadhesin Enhances Phagocytosis of Pneumocystis carinii by Human Polymorphonuclear Leukocytes In Vitro

Cited by 19 publications

References 32 publications

N -Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

N -Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

Effect of Transcription Factor GATA-2 on Phagocytic Activity of Alveolar Macrophages fromPneumocystis carinii-Infected Hosts

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