The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
David L Williams - One of the best experts on this subject based on the ideXlab platform.
-
Recognition of fungal Glucans by pattern recognition receptors.
2003Co-Authors: David L Williams, R. Rice, Jurgen Herre, Janet A. Willment, Philip R. Taylor, P. R. Gordon, Gordon D BrownAbstract:Glucans are (1→3)-β-D linked polymers of glucose that are major constituents of fungal cells walls. Glucans are known to stimulate innate immunity and they are thought to be fungal pathogen associated molecular patterns. Several recent discoveries have dramatically increased our knowledge of the cellular and molecular biology of Glucans. Among the most significant advances has been the identification and characterization of Glucan specific pattern recognition receptors. This review examines the recent data on the identity, cellular distribution and binding interactions of receptors that recognize fungal Glucans. Specific emphasis is placed on the role of Dectin-1 and scavenger receptors as Glucan binding sites. The definitive identification and characterization of Glucan specific receptors is an essential prerequisite for deciphering the cellular and molecular interactions of fungal Glucans with the innate immune system
-
human monocyte scavenger receptors are pattern recognition receptors for 1 3 β d Glucans
Journal of Leukocyte Biology, 2002Co-Authors: Peter J Rice, John Kalbfleisch, David L Williams, Harry E Ensley, Grigorij Kogan, Jim Kelley, William I BrowderAbstract:Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plas- mon resonance to examine the binding of Glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the in- teraction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phos- phate interacts with all sites, and the CM-Glucans and laminarin interact with a subset of sites. Poly- mer charge has a dramatic effect on the affinity of Glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic Glucan structure independent of charge. J. Leukoc. Biol. 72: 140-146; 2002.
-
the influence of Glucan polymer structure and solution conformation on binding to 1 3 β d Glucan receptors in a human monocyte like cell line
Glycobiology, 2000Co-Authors: Antje Mueller, John Raptis, Robert D Stout, William Browder, Peter J Rice, John Kalbfleisch, Harry E Ensley, David L WilliamsAbstract:: Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-Glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-Glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-Glucan binding, since mannan, dextran, or barley Glucan did not bind. ScleroGlucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-Glucan polymers examined. The rank order competitive binding affinities for the Glucan polymers were scleroGlucan>>>schizophyllan > laminarin > Glucan phosphate > Glucan sulfate. ScleroGlucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. ScleroGlucan and Glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-Glucans and that the triple helical solution conformation, molecular weight and charge of the Glucan polymer may be important determinants in receptor ligand interaction.
Gordon D Brown - One of the best experts on this subject based on the ideXlab platform.
-
β Glucans and dectin 1
Annals of the New York Academy of Sciences, 2008Co-Authors: Vicky S Tsoni, Gordon D BrownAbstract:beta-Glucans are naturally occurring carbohydrates that possess immune-modulating activities, but their mechanisms of action are largely unknown. Recent discoveries, however, including identification of beta-Glucan receptors, such as dectin-1, have started to shed some light on the mechanisms underlying the properties of these carbohydrates. The characterization of dectin-1, in particular, has revealed some of the processes involved in beta-Glucan sensing, intracellular signaling, and induction of cellular responses and has provided new insights into the role of beta-Glucans in immunity and disease. Here we review both beta-Glucans and their receptor, dectin-1.
-
differential high affinity interaction of dectin 1 with natural or synthetic Glucans is dependent upon primary structure and is influenced by polymer chain length and side chain branching
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Elizabeth L Adams, Peter J Rice, Harry E Ensley, Bridget M Graves, Gordon D Brown, Siamon Gordon, Mario A Monteiro, Erzsebet Pappszabo, Douglas W Lowman, Trevor D PowerAbstract:Glucans are structurally diverse fungal biopolymers that stimulate innate immunity and are fungal pathogen-associated molecular patterns. Dectin-1 is a C-type lectin-like pattern recognition receptor that binds Glucans and induces innate immune responses to fungal pathogens. We examined the effect of Glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1-->3)-beta/(1-->6)-beta-Glucans as well as nonGlucan polymers. Dectin-1 is highly specific for Glucans with a pure (1-->3)-beta-linked backbone structure. Although Dectin-1 is highly specific for (1-->3)-beta-d-Glucans, it does not recognize all Glucans equally. Dectin-1 differentially interacted with (1-->3)-beta-d-Glucans over a very wide range of binding affinities (2.6 mM-2.2 pM). One of the most striking observations that emerged from this study was the remarkable high-affinity interaction of Dectin-1 with certain Glucans (2.2 pM). These data also demonstrated that synthetic Glucan ligands interact with Dectin-1 and that binding affinity increased in synthetic Glucans containing a single glucose side-chain branch. We also observed differential recognition of Glucans derived from saprophytes and pathogens. We found that Glucan derived from a saprophytic yeast was recognized with higher affinity than Glucan derived from the pathogen Candida albicans. Structural analysis demonstrated that Glucan backbone chain length and (1-->6)-beta side-chain branching strongly influenced Dectin-1 binding affinity. These data demonstrate: 1) the specificity of Dectin-1 for Glucans; 2) that Dectin-1 differentiates between Glucan ligands based on structural determinants; and 3) that Dectin-1 can recognize and interact with both natural product and synthetic Glucan ligands.
-
β‐Glucans and Dectin‐1
Annals of the New York Academy of Sciences, 2008Co-Authors: S. Vicky Tsoni, Gordon D BrownAbstract:beta-Glucans are naturally occurring carbohydrates that possess immune-modulating activities, but their mechanisms of action are largely unknown. Recent discoveries, however, including identification of beta-Glucan receptors, such as dectin-1, have started to shed some light on the mechanisms underlying the properties of these carbohydrates. The characterization of dectin-1, in particular, has revealed some of the processes involved in beta-Glucan sensing, intracellular signaling, and induction of cellular responses and has provided new insights into the role of beta-Glucans in immunity and disease. Here we review both beta-Glucans and their receptor, dectin-1.
-
Recognition of fungal Glucans by pattern recognition receptors.
2003Co-Authors: David L Williams, R. Rice, Jurgen Herre, Janet A. Willment, Philip R. Taylor, P. R. Gordon, Gordon D BrownAbstract:Glucans are (1→3)-β-D linked polymers of glucose that are major constituents of fungal cells walls. Glucans are known to stimulate innate immunity and they are thought to be fungal pathogen associated molecular patterns. Several recent discoveries have dramatically increased our knowledge of the cellular and molecular biology of Glucans. Among the most significant advances has been the identification and characterization of Glucan specific pattern recognition receptors. This review examines the recent data on the identity, cellular distribution and binding interactions of receptors that recognize fungal Glucans. Specific emphasis is placed on the role of Dectin-1 and scavenger receptors as Glucan binding sites. The definitive identification and characterization of Glucan specific receptors is an essential prerequisite for deciphering the cellular and molecular interactions of fungal Glucans with the innate immune system
Peter J Rice - One of the best experts on this subject based on the ideXlab platform.
-
differential high affinity interaction of dectin 1 with natural or synthetic Glucans is dependent upon primary structure and is influenced by polymer chain length and side chain branching
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Elizabeth L Adams, Peter J Rice, Harry E Ensley, Bridget M Graves, Gordon D Brown, Siamon Gordon, Mario A Monteiro, Erzsebet Pappszabo, Douglas W Lowman, Trevor D PowerAbstract:Glucans are structurally diverse fungal biopolymers that stimulate innate immunity and are fungal pathogen-associated molecular patterns. Dectin-1 is a C-type lectin-like pattern recognition receptor that binds Glucans and induces innate immune responses to fungal pathogens. We examined the effect of Glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1-->3)-beta/(1-->6)-beta-Glucans as well as nonGlucan polymers. Dectin-1 is highly specific for Glucans with a pure (1-->3)-beta-linked backbone structure. Although Dectin-1 is highly specific for (1-->3)-beta-d-Glucans, it does not recognize all Glucans equally. Dectin-1 differentially interacted with (1-->3)-beta-d-Glucans over a very wide range of binding affinities (2.6 mM-2.2 pM). One of the most striking observations that emerged from this study was the remarkable high-affinity interaction of Dectin-1 with certain Glucans (2.2 pM). These data also demonstrated that synthetic Glucan ligands interact with Dectin-1 and that binding affinity increased in synthetic Glucans containing a single glucose side-chain branch. We also observed differential recognition of Glucans derived from saprophytes and pathogens. We found that Glucan derived from a saprophytic yeast was recognized with higher affinity than Glucan derived from the pathogen Candida albicans. Structural analysis demonstrated that Glucan backbone chain length and (1-->6)-beta side-chain branching strongly influenced Dectin-1 binding affinity. These data demonstrate: 1) the specificity of Dectin-1 for Glucans; 2) that Dectin-1 differentiates between Glucan ligands based on structural determinants; and 3) that Dectin-1 can recognize and interact with both natural product and synthetic Glucan ligands.
-
oral delivery and gastrointestinal absorption of soluble Glucans stimulate increased resistance to infectious challenge
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Peter J Rice, Elizabeth L Adams, Tammy Ozmentskelton, Andres J Gonzalez, Matthew P Goldman, Brent E Lockhart, Luke A Barker, Kevin F Breuel, Warren K Deponti, John KalbfleischAbstract:Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble Glucans (Glucan phosphate, laminarin, and scleroGlucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for Glucan phosphate occurred at 4 h. In contrast, laminarin and scleroGlucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 +/- 3% of the Glucan phosphate and 20 +/- 7% of the laminarin remained in the serum. ScleroGlucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma Glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, Glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of Glucan by intestinal epithelial cells was not Dectin-dependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of Glucan. Oral Glucan increased systemic levels of interleukin (IL)-12 (151 +/- 15%) in mice. Oral Glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble Glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The Glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.
-
human monocyte scavenger receptors are pattern recognition receptors for 1 3 β d Glucans
Journal of Leukocyte Biology, 2002Co-Authors: Peter J Rice, John Kalbfleisch, David L Williams, Harry E Ensley, Grigorij Kogan, Jim Kelley, William I BrowderAbstract:Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plas- mon resonance to examine the binding of Glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the in- teraction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phos- phate interacts with all sites, and the CM-Glucans and laminarin interact with a subset of sites. Poly- mer charge has a dramatic effect on the affinity of Glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic Glucan structure independent of charge. J. Leukoc. Biol. 72: 140-146; 2002.
-
the influence of Glucan polymer structure and solution conformation on binding to 1 3 β d Glucan receptors in a human monocyte like cell line
Glycobiology, 2000Co-Authors: Antje Mueller, John Raptis, Robert D Stout, William Browder, Peter J Rice, John Kalbfleisch, Harry E Ensley, David L WilliamsAbstract:: Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-Glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-Glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-Glucan binding, since mannan, dextran, or barley Glucan did not bind. ScleroGlucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-Glucan polymers examined. The rank order competitive binding affinities for the Glucan polymers were scleroGlucan>>>schizophyllan > laminarin > Glucan phosphate > Glucan sulfate. ScleroGlucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. ScleroGlucan and Glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-Glucans and that the triple helical solution conformation, molecular weight and charge of the Glucan polymer may be important determinants in receptor ligand interaction.
Geoffrey B. Fincher - One of the best experts on this subject based on the ideXlab platform.
-
1 3 1 4 β d Glucans in cell walls of the poaceae lower plants and fungi a tale of two linkages
Molecular Plant, 2009Co-Authors: Rachel A Burton, Geoffrey B. FincherAbstract:(1,3;1,4)-β-D-Glucans consist of unbranched and unsubstituted chains of (1,3)- and (1,4)-β-glucosyl residues, in which the ratio of (1,4)-β-D-glucosyl residues to (1,3)-β-D-glucosyl residues appears to influence not only the physicochemical properties of the polysaccharide and therefore its functional properties in cell walls, but also its adoption by different plant species during evolution. The (1,3;1,4)-β-D-Glucans are widely distributed as non-cellulosic matrix phase polysaccharides in cell walls of the Poaceae, which evolved relatively recently and consist of the grasses and commercially important cereal species, but they are less commonly found in lower vascular plants, such as the horsetails, in algae and in fungi. The (1,3;1,4)-β-D-Glucans have often been considered to be components mainly of primary cell walls, but recent observations indicate that they can also be located in secondary walls of certain tissues. Enzymes involved in the depolymerisation of (1,3;1,4)-β-D-Glucans have been well characterized. In contrast, initial difficulties in purifying the enzymes responsible for (1,3;1,4)-β-D-Glucan biosynthesis slowed progress in the identification of the genes that encode (1,3;1,4)-β-D-Glucan synthases, but emerging comparative genomics and associated techniques have allowed at least some of the genes that contribute to (1,3;1,4)-β-D-Glucan synthesis in the Poaceae to be identified. Whether similar genes and enzymes also mediate (1,3;1,4)-β-D-Glucan biosynthesis in lower plants and fungi is not yet known. Here, we compare the different fine structures of (1,3;1,4)-β-D-Glucans across the plant kingdom, present current information on the genes that have been implicated recently in their biosynthesis, and consider aspects of the cell biology of (1,3;1,4)-β-D-Glucan biosynthesis in the Poaceae.
-
A Barley XyloGlucan Xyloglucosyl Transferase Covalently Links XyloGlucan, Cellulosic Substrates, and (1,3;1,4)-β-D-Glucans
The Journal of biological chemistry, 2007Co-Authors: Maria Hrmova, Vladimir Farkas, Jelle Lahnstein, Geoffrey B. FincherAbstract:Abstract Molecular interactions between wall polysaccharides, which include cellulose and a range of noncellulosic polysaccharides such as xyloGlucans and (1,3;1,4)-β-d-Glucans, are fundamental to cell wall properties. These interactions have been assumed to be noncovalent in nature in most cases. Here we show that a highly purified barley xyloGlucan xyloglucosyl transferase HvXET5 (EC 2.4.1.207), a member of the GH16 group of glycoside hydrolases, catalyzes the in vitro formation of covalent linkages between xyloGlucans and cellulosic substrates and between xyloGlucans and (1,3;1,4)-β-d-Glucans. The rate of covalent bond formation catalyzed by HvXET5 with hydroxyethylcellulose (HEC) is comparable with that on tamarind xyloGlucan, whereas that with (1,3; 1,4)-β-d-Glucan is significant but slower. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analyses showed that oligosaccharides released from the fluorescent HEC:xyloGlucan conjugate by a specific (1,4)-β-dGlucan endohydrolase consisted of xyloGlucan substrate with one, two, or three glucosyl residues attached. Ancillary peaks contained hydroxyethyl substituents (m/z 45) and confirmed that the parent material consisted of HEC covalently linked with xyloGlucan. Similarly, partial hydrolysis of the (1,3;1,4)-β-d-Glucan:xyloGlucan conjugate by a specific (1,3;1,4)-β-d-Glucan endohydrolase revealed the presence of a series of fluorescent oligosaccharides that consisted of the fluorescent xyloGlucan acceptor substrate linked covalently with 2-6 glucosyl residues. These findings raise the possibility that xyloGlucan endo-transglucosylases could link different polysaccharides in vivo and hence influence cell wall strength, flexibility, and porosity.
-
cellulose synthase like cslf genes mediate the synthesis of cell wall 1 3 1 4 beta d Glucans
Science, 2006Co-Authors: Rachel A Burton, Bruce A. Stone, Maria Hrmova, Neil J Shirley, Sally Wilson, Andrew Harvey, Anne Medhurst, Ed Newbigin, Antony Bacic, Geoffrey B. FincherAbstract:A characteristic feature of grasses and commercially important cereals is the presence of (1,3;1,4)-beta-d-Glucans in their cell walls. We have used comparative genomics to link a major quantitative trait locus for (1,3;1,4)-beta-d-Glucan content in barley grain to a cluster of cellulose synthase-like CslF genes in rice. After insertion of rice CslF genes into Arabidopsis, we detected (1,3;1,4)-beta-d-Glucan in walls of transgenic plants using specific monoclonal antibodies and enzymatic analysis. Because wild-type Arabidopsis does not contain CslF genes or have (1,3;1,4)-beta-d-Glucans in its walls, these experiments provide direct, gain-of-function evidence for the participation of rice CslF genes in (1,3;1,4)-beta-d-Glucan biosynthesis.
Harry E Ensley - One of the best experts on this subject based on the ideXlab platform.
-
novel structural features in candida albicans hyphal Glucan provide a basis for differential innate immune recognition of hyphae versus yeast
Journal of Biological Chemistry, 2014Co-Authors: Harry E Ensley, Mario A Monteiro, Douglas W Lowman, Rachel R Greene, Daniel W Bearden, Michael D Kruppa, Max Pottier, D V Soldatov, Shihchin ChengAbstract:The innate immune system differentially recognizes Candida albicans yeast and hyphae. It is not clear how the innate immune system effectively discriminates between yeast and hyphal forms of C. albicans. Glucans are major components of the fungal cell wall and key fungal pathogen-associated molecular patterns. C. albicans yeast Glucan has been characterized; however, little is known about Glucan structure in C. albicans hyphae. Using an extraction procedure that minimizes degradation of the native structure, we extracted Glucans from C. albicans hyphal cell walls. 1H NMR data analysis revealed that, when compared with reference (1→3,1→6) β-linked Glucans and C. albicans yeast Glucan, hyphal Glucan has a unique cyclical or “closed chain” structure that is not found in yeast Glucan. GC/MS analyses showed a high abundance of 3- and 6-linked glucose units when compared with yeast β-Glucan. In addition to the expected (1→3), (1→6), and 3,6 linkages, we also identified a 2,3 linkage that has not been reported previously in C. albicans. Hyphal Glucan induced robust immune responses in human peripheral blood mononuclear cells and macrophages via a Dectin-1-dependent mechanism. In contrast, C. albicans yeast Glucan was a much less potent stimulus. We also demonstrated the capacity of C. albicans hyphal Glucan, but not yeast Glucan, to induce IL-1β processing and secretion. This finding provides important evidence for understanding the immune discrimination between colonization and invasion at the mucosal level. When taken together, these data provide a structural basis for differential innate immune recognition of C. albicans yeast versus hyphae.
-
differential high affinity interaction of dectin 1 with natural or synthetic Glucans is dependent upon primary structure and is influenced by polymer chain length and side chain branching
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Elizabeth L Adams, Peter J Rice, Harry E Ensley, Bridget M Graves, Gordon D Brown, Siamon Gordon, Mario A Monteiro, Erzsebet Pappszabo, Douglas W Lowman, Trevor D PowerAbstract:Glucans are structurally diverse fungal biopolymers that stimulate innate immunity and are fungal pathogen-associated molecular patterns. Dectin-1 is a C-type lectin-like pattern recognition receptor that binds Glucans and induces innate immune responses to fungal pathogens. We examined the effect of Glucan structure on recognition and binding by murine recombinant Dectin-1 with a library of natural product and synthetic (1-->3)-beta/(1-->6)-beta-Glucans as well as nonGlucan polymers. Dectin-1 is highly specific for Glucans with a pure (1-->3)-beta-linked backbone structure. Although Dectin-1 is highly specific for (1-->3)-beta-d-Glucans, it does not recognize all Glucans equally. Dectin-1 differentially interacted with (1-->3)-beta-d-Glucans over a very wide range of binding affinities (2.6 mM-2.2 pM). One of the most striking observations that emerged from this study was the remarkable high-affinity interaction of Dectin-1 with certain Glucans (2.2 pM). These data also demonstrated that synthetic Glucan ligands interact with Dectin-1 and that binding affinity increased in synthetic Glucans containing a single glucose side-chain branch. We also observed differential recognition of Glucans derived from saprophytes and pathogens. We found that Glucan derived from a saprophytic yeast was recognized with higher affinity than Glucan derived from the pathogen Candida albicans. Structural analysis demonstrated that Glucan backbone chain length and (1-->6)-beta side-chain branching strongly influenced Dectin-1 binding affinity. These data demonstrate: 1) the specificity of Dectin-1 for Glucans; 2) that Dectin-1 differentiates between Glucan ligands based on structural determinants; and 3) that Dectin-1 can recognize and interact with both natural product and synthetic Glucan ligands.
-
human monocyte scavenger receptors are pattern recognition receptors for 1 3 β d Glucans
Journal of Leukocyte Biology, 2002Co-Authors: Peter J Rice, John Kalbfleisch, David L Williams, Harry E Ensley, Grigorij Kogan, Jim Kelley, William I BrowderAbstract:Glucans are cell wall constituents of fungi and bacteria that bind to pattern recognition receptors and modulate innate immunity, in part, by macrophage activation. We used surface plas- mon resonance to examine the binding of Glucans, differing in fine structure and charge density, to scavenger receptors on membranes isolated from human monocyte U937 cells. Experiments were performed at 25°C using a biosensor surface with immobilized acetylated low density lipoprotein (AcLDL). Inhibition of the binding by polyinosinic acid, but not polycytidylic acid, confirmed the in- teraction of scavenger receptors. Competition studies showed that there are at least two AcLDL binding sites on human U937 cells. Glucan phos- phate interacts with all sites, and the CM-Glucans and laminarin interact with a subset of sites. Poly- mer charge has a dramatic effect on the affinity of Glucans with macrophage scavenger receptors. However, it is also clear that human monocyte scavenger receptors recognize the basic Glucan structure independent of charge. J. Leukoc. Biol. 72: 140-146; 2002.
-
the influence of Glucan polymer structure and solution conformation on binding to 1 3 β d Glucan receptors in a human monocyte like cell line
Glycobiology, 2000Co-Authors: Antje Mueller, John Raptis, Robert D Stout, William Browder, Peter J Rice, John Kalbfleisch, Harry E Ensley, David L WilliamsAbstract:: Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-Glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-Glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-Glucan binding, since mannan, dextran, or barley Glucan did not bind. ScleroGlucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-Glucan polymers examined. The rank order competitive binding affinities for the Glucan polymers were scleroGlucan>>>schizophyllan > laminarin > Glucan phosphate > Glucan sulfate. ScleroGlucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. ScleroGlucan and Glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-Glucans and that the triple helical solution conformation, molecular weight and charge of the Glucan polymer may be important determinants in receptor ligand interaction.