The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Usha Chakravarthy - One of the best experts on this subject based on the ideXlab platform.
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Higher plasma levels of complement C3a, C4A and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha Chakravarthy, Heping XuAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case–control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4A and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4A and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4A and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. Conclusions Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
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higher plasma levels of complement c3a C4A and c5a increase the risk of subretinal fibrosis in neovascular age related macular degeneration complement activation in amd
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha ChakravarthyAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy.
Judith Lechner - One of the best experts on this subject based on the ideXlab platform.
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Higher plasma levels of complement C3a, C4A and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha Chakravarthy, Heping XuAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case–control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4A and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4A and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4A and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. Conclusions Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
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higher plasma levels of complement c3a C4A and c5a increase the risk of subretinal fibrosis in neovascular age related macular degeneration complement activation in amd
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha ChakravarthyAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy.
Peter N Monk - One of the best experts on this subject based on the ideXlab platform.
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international union of basic and clinical pharmacology lxxxvii complement peptide c5a C4A and c3a receptors
Pharmacological Reviews, 2013Co-Authors: Andreas Klos, Elisabeth Wende, Kathryn J Wareham, Peter N MonkAbstract:The activation of the complement cascade, a cornerstone of the innate immune response, produces a number of small (74–77 amino acid) fragments, originally termed anaphylatoxins, that are potent chemoattractants and secretagogues that act on a wide variety of cell types. These fragments, C5a, C4A, and C3a, participate at all levels of the immune response and are also involved in other processes such as neural development and organ regeneration. Their primary function, however, is in inflammation, so they are important targets for the development of anti-inflammatory therapies. Only three receptors for complement peptides have been found, but there are no satisfactory antagonists as yet, despite intensive investigation. In humans, there is a single receptor for C3a (C3a receptor), no known receptor for C4A, and two receptors for C5a (C5a1 receptor and C5a2 receptor). The most recently characterized receptor, the C5a2 receptor (previously known as C5L2 or GPR77), has been regarded as a passive binding protein, but signaling activities are now ascribed to it, so we propose that it be formally identified as a receptor and be given a name to reflect this. Here, we describe the complex biology of the complement peptides, introduce a new suggested nomenclature, and review our current knowledge of receptor pharmacology.
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the chemoattractant receptor like protein c5l2 binds the c3a des arg77 acylation stimulating protein
Journal of Biological Chemistry, 2003Co-Authors: David Kalant, Stuart A Cain, Katherine Cianflone, Magdalena Maslowska, Allan D. Sniderman, Peter N MonkAbstract:Abstract The orphan receptor C5L2 has recently been described as a high affinity binding protein for complement fragments C5a and C3a that, unlike the previously described C5a receptor (CD88), couples only weakly to Gi-like G proteins (Cain, S. A., and Monk, P. N. (2002) J. Biol. Chem. 277, 7165–7169). Here we demonstrate that C5L2 binds the metabolites of C4A and C3a, C4A des-Arg77, and C3a des-Arg77 (also known as the acylation-stimulating protein or ASP) at a site distinct from the C5a binding site. The binding of these metabolites to C5L2 does not stimulate the degranulation of transfected rat basophilic leukemia cells either through endogenous rat G proteins or when co-transfected with human Gα16. C3a des-Arg77/ASP and C3a can potently stimulate triglyceride synthesis in human skin fibroblasts and 3T3-L1 preadipocytes. Here we show that both cell types and human adipose tissue express C5L2 mRNA and that the human fibroblasts express C5L2 protein at the cell surface. This is the first demonstration of the expression of C5L2 in cells that bind and respond to C3a des-Arg77/ASP and C3a. Thus C5L2, a promiscuous complement fragment-binding protein with a high affinity site that binds C3a des-Arg77/ASP, may mediate the acylation-stimulating properties of this peptide.
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The Chemoattractant Receptor-like Protein C5L2 Binds the C3a des-Arg77/Acylation-stimulating Protein
The Journal of biological chemistry, 2003Co-Authors: David Kalant, Stuart A Cain, Katherine Cianflone, Magdalena Maslowska, Allan D. Sniderman, Peter N MonkAbstract:Abstract The orphan receptor C5L2 has recently been described as a high affinity binding protein for complement fragments C5a and C3a that, unlike the previously described C5a receptor (CD88), couples only weakly to Gi-like G proteins (Cain, S. A., and Monk, P. N. (2002) J. Biol. Chem. 277, 7165–7169). Here we demonstrate that C5L2 binds the metabolites of C4A and C3a, C4A des-Arg77, and C3a des-Arg77 (also known as the acylation-stimulating protein or ASP) at a site distinct from the C5a binding site. The binding of these metabolites to C5L2 does not stimulate the degranulation of transfected rat basophilic leukemia cells either through endogenous rat G proteins or when co-transfected with human Gα16. C3a des-Arg77/ASP and C3a can potently stimulate triglyceride synthesis in human skin fibroblasts and 3T3-L1 preadipocytes. Here we show that both cell types and human adipose tissue express C5L2 mRNA and that the human fibroblasts express C5L2 protein at the cell surface. This is the first demonstration of the expression of C5L2 in cells that bind and respond to C3a des-Arg77/ASP and C3a. Thus C5L2, a promiscuous complement fragment-binding protein with a high affinity site that binds C3a des-Arg77/ASP, may mediate the acylation-stimulating properties of this peptide.
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the orphan receptor c5l2 has high affinity binding sites for complement fragments c5a and c5a des arg 74
Journal of Biological Chemistry, 2002Co-Authors: Stuart A Cain, Peter N MonkAbstract:Abstract The substantial variations in the responses of cells to the anaphylatoxin C5a and its desarginated form, C5adR74, suggest that more than one type of cell surface receptor for these ligands might exist. However, only a single receptor for C5a and C5adR74, CD88, has been characterized to date. Here we report that the orphan receptor C5L2/gpr77, which shares 35% amino acid identity with CD88, binds C5a with high affinity but has a 10-fold higher affinity for C5adR74 than CD88. C5L2 also has a moderate affinity for anaphylatoxin C3a, but cross-competition studies suggest that C3a binds to a distinct site from C5a. C4A was able to displace C3a, suggesting that C5L2, like the C3a receptor, may have a low binding affinity for this anaphylatoxin. Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca2+] and is not rapidly internalized in response to ligand binding. However, ligation of C5L2 by anaphylatoxin did potentiate the degranulation response to cross-linkage of the high affinity IgE receptor by a pertussis toxin-sensitive mechanism. These results suggest that C5L2 is an anaphylatoxin-binding protein with unique ligand binding and signaling properties.
Giuliana Silvestri - One of the best experts on this subject based on the ideXlab platform.
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Higher plasma levels of complement C3a, C4A and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha Chakravarthy, Heping XuAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case–control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4A and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4A and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4A and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. Conclusions Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
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higher plasma levels of complement c3a C4A and c5a increase the risk of subretinal fibrosis in neovascular age related macular degeneration complement activation in amd
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha ChakravarthyAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy.
Levente Toth - One of the best experts on this subject based on the ideXlab platform.
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Higher plasma levels of complement C3a, C4A and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha Chakravarthy, Heping XuAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy. Results Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case–control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4A and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4A and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4A and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. Conclusions Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
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higher plasma levels of complement c3a C4A and c5a increase the risk of subretinal fibrosis in neovascular age related macular degeneration complement activation in amd
Immunity & Ageing, 2016Co-Authors: Judith Lechner, Mei Chen, Ruth E. Hogg, Levente Toth, Giuliana Silvestri, Usha ChakravarthyAbstract:Background The aim of this study was to investigate the plasma levels of complement C3a, C4A, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients’ responsiveness to anti-VEGF therapy.