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Volumn 184, Issue 2, 1996, Pages 585-595

Activation of phospholipase D is tightly coupled to the phagocytosis of Mycobacterium tuberculosis or opsonized zymosan by human macrophages

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; PHOSPHATIDIC ACID; PHOSPHOLIPASE D;

EID: 0029841123     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.184.2.585     Document Type: Article
Times cited : (89)

References (46)
  • 1
    • 0003082670 scopus 로고
    • Epidemiology of Tuberculosis
    • B.R. Bloom, editor. American Society for Microbiology, Washington, D.C.
    • Smith, P.E., and A.R. Moss. 1994. Epidemiology of Tuberculosis. In Tuberculosis: Pathogenesis, Protection, and Control. B.R. Bloom, editor. American Society for Microbiology, Washington, D.C. 47-60.
    • (1994) Tuberculosis: Pathogenesis, Protection, and Control , pp. 47-60
    • Smith, P.E.1    Moss, A.R.2
  • 2
    • 0003083309 scopus 로고
    • Mechanisms of pathogenesis in tuberculosis
    • B.R. Bloom, editor. ASM, Washington, D.C.
    • Rook, G.A.W., and B.R. Bloom. 1994. Mechanisms of pathogenesis in tuberculosis. In Tuberculosis: Pathogenesis, Protection, and Control. B.R. Bloom, editor. ASM, Washington, D.C. 485-502.
    • (1994) Tuberculosis: Pathogenesis, Protection, and Control , pp. 485-502
    • Rook, G.A.W.1    Bloom, B.R.2
  • 3
    • 0025216480 scopus 로고
    • Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3
    • Schlesinger, L.S., C.G. Bellinger-Kawahara, N.R. Payne, and M.A. Horwitz. 1990. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J. Immunol. 144:2771-2780.
    • (1990) J. Immunol. , vol.144 , pp. 2771-2780
    • Schlesinger, L.S.1    Bellinger-Kawahara, C.G.2    Payne, N.R.3    Horwitz, M.A.4
  • 4
    • 0027173039 scopus 로고
    • Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors
    • Schlesinger, L.S. 1993. Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. J. Immunol. 150:2920-2930.
    • (1993) J. Immunol. , vol.150 , pp. 2920-2930
    • Schlesinger, L.S.1
  • 5
    • 0028349268 scopus 로고
    • Complement receptor-mediated uptake and tumor necrosis factor-α-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages
    • Hirsch, C.S., J.J. Ellner, D.G. Russell, and E.A. Rich. 1994. Complement receptor-mediated uptake and tumor necrosis factor-α-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 152:743-753.
    • (1994) J. Immunol. , vol.152 , pp. 743-753
    • Hirsch, C.S.1    Ellner, J.J.2    Russell, D.G.3    Rich, E.A.4
  • 7
    • 0002553601 scopus 로고
    • Receptors for complement and the biology of phagocytosis
    • J.I. Gallin, I.M. Goldstein, and R. Snyderman, editors. Raven Press, Ltd., New York
    • Wright, S.D. 1992. Receptors for complement and the biology of phagocytosis. In Inflammation: Basic Principles and Clinical Correlates. Second Edition. J.I. Gallin, I.M. Goldstein, and R. Snyderman, editors. Raven Press, Ltd., New York. 477-501.
    • (1992) Inflammation: Basic Principles and Clinical Correlates. Second Edition , pp. 477-501
    • Wright, S.D.1
  • 8
    • 0026788406 scopus 로고
    • Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidycholine-derived diglyceride in human neutrophils
    • Fallman, M., M. Gullberg, C. Hellberg, and T. Andersson. 1992. Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidycholine-derived diglyceride in human neutrophils. J. Biol. Chem. 267:2656-2663.
    • (1992) J. Biol. Chem. , vol.267 , pp. 2656-2663
    • Fallman, M.1    Gullberg, M.2    Hellberg, C.3    Andersson, T.4
  • 9
    • 0024434289 scopus 로고
    • Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol
    • Fallman, M., D.P. Lew, O. Stendahl, and T. Andersson. 1989. Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. J. Clin. Invest. 84:886-891.
    • (1989) J. Clin. Invest. , vol.84 , pp. 886-891
    • Fallman, M.1    Lew, D.P.2    Stendahl, O.3    Andersson, T.4
  • 10
    • 0021080912 scopus 로고
    • Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes
    • Wright, S.D., and S.C. Silverstein. 1983. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J. Exp. Med. 158:2016-2023.
    • (1983) J. Exp. Med. , vol.158 , pp. 2016-2023
    • Wright, S.D.1    Silverstein, S.C.2
  • 11
    • 0021328346 scopus 로고
    • Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages
    • Yamamoto, K., and R.B. Johnston, Jr. 1984. Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages. J. Exp. Med. 159:405-416.
    • (1984) J. Exp. Med. , vol.159 , pp. 405-416
    • Yamamoto, K.1    Johnston Jr., R.B.2
  • 12
    • 0027292168 scopus 로고
    • Signaling properties of CR3 (CD11b/CD18) and CR1 (CD35) in relation to phagocytosis of complement-opsonized particles
    • Fallman, M., R. Andersson, and T. Andersson. 1993. Signaling properties of CR3 (CD11b/CD18) and CR1 (CD35) in relation to phagocytosis of complement-opsonized particles. J. Immunol. 151:330-338.
    • (1993) J. Immunol. , vol.151 , pp. 330-338
    • Fallman, M.1    Andersson, R.2    Andersson, T.3
  • 13
    • 0024849693 scopus 로고
    • Platelet-activating factor enhances complement-dependent phagocytosis - Of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1)
    • Bussolino, F., E. Fischer, F. Turrini, M.D. Kazatchkine, and P. Arese. 1989. Platelet-activating factor enhances complement-dependent phagocytosis - of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1). J. Biol. Chem. 264:21711-21719.
    • (1989) J. Biol. Chem. , vol.264 , pp. 21711-21719
    • Bussolino, F.1    Fischer, E.2    Turrini, F.3    Kazatchkine, M.D.4    Arese, P.5
  • 14
    • 0029162389 scopus 로고
    • A role for MARCKS, the α isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages
    • Allen, L.H., and A. Aderem. 1995. A role for MARCKS, the α isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages. J. Exp. Med. 182:829-840.
    • (1995) J. Exp. Med. , vol.182 , pp. 829-840
    • Allen, L.H.1    Aderem, A.2
  • 15
    • 0024366057 scopus 로고
    • Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils
    • Billah, M.M., S. Eckel, T.J. Mullmann, R.W. Egan, and M.I. Siegel. 1989. Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. J. Biol. Chem. 264:17069-17075.
    • (1989) J. Biol. Chem. , vol.264 , pp. 17069-17075
    • Billah, M.M.1    Eckel, S.2    Mullmann, T.J.3    Egan, R.W.4    Siegel, M.I.5
  • 16
    • 0027403699 scopus 로고
    • Phospholipase D and cell signalling
    • Billah, M.M. 1993. Phospholipase D and cell signalling. Curr. Opin. Immunol. 5:114-123.
    • (1993) Curr. Opin. Immunol. , vol.5 , pp. 114-123
    • Billah, M.M.1
  • 17
    • 0020661110 scopus 로고
    • A simple method for counting adherent cells: Application to cultured human monocytes and multinucleated giant cells
    • Nakagawara, A., and C.F. Nathan. 1983. A simple method for counting adherent cells: application to cultured human monocytes and multinucleated giant cells. J. Immunol. Methods. 56:261-268.
    • (1983) J. Immunol. Methods , vol.56 , pp. 261-268
    • Nakagawara, A.1    Nathan, C.F.2
  • 18
    • 0027142022 scopus 로고
    • ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity
    • Brown, H.A., S. Gutowski, C.R. Moomaw, C. Slaughter, and P.C. Sternweis. 1993. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Cell. 75:1137-1144.
    • (1993) Cell , vol.75 , pp. 1137-1144
    • Brown, H.A.1    Gutowski, S.2    Moomaw, C.R.3    Slaughter, C.4    Sternweis, P.C.5
  • 19
    • 0028832349 scopus 로고
    • Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobaterium tuberculosis by a direct interaction with human macrophages
    • Gaynor, C., F.X. McCormack, D.R. Voelker, S.E. McGowan, and L.S. Schlesinger. 1995. Pulmonary surfactant protein A mediates enhanced phagocytosis of Mycobaterium tuberculosis by a direct interaction with human macrophages. J. Immunol. 155:5343-5351.
    • (1995) J. Immunol. , vol.155 , pp. 5343-5351
    • Gaynor, C.1    McCormack, F.X.2    Voelker, D.R.3    McGowan, S.E.4    Schlesinger, L.S.5
  • 20
    • 0020661782 scopus 로고
    • Yeast mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages
    • Sun-Sang, J., R.S. Nelson, and S.C. Silverstein. 1983. Yeast mannans inhibit binding and phagocytosis of zymosan by mouse peritoneal macrophages. J. Cell Biol. 96:160-166.
    • (1983) J. Cell Biol. , vol.96 , pp. 160-166
    • Sun-Sang, J.1    Nelson, R.S.2    Silverstein, S.C.3
  • 21
    • 0025946883 scopus 로고
    • Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-γ activation inhibits complement receptor function and phagocytosis of this bacterium
    • Schlesinger, L.S., and M.A. Horwitz. 1991. Phagocytosis of Mycobacterium leprae by human monocyte-derived macrophages is mediated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) and IFN-γ activation inhibits complement receptor function and phagocytosis of this bacterium. J. Immunol. 147:1983-1994.
    • (1991) J. Immunol. , vol.147 , pp. 1983-1994
    • Schlesinger, L.S.1    Horwitz, M.A.2
  • 22
    • 0029076020 scopus 로고
    • MacMARCKS mutation blocks macrophage phagocytosis of zymosan
    • Zhu, Z., Z. Bao, and J. Li. 1995. MacMARCKS mutation blocks macrophage phagocytosis of zymosan. J. Exp. Med. 270:17652-17655.
    • (1995) J. Exp. Med. , vol.270 , pp. 17652-17655
    • Zhu, Z.1    Bao, Z.2    Li, J.3
  • 23
    • 0021345152 scopus 로고
    • Local opsonization by secreted macrophage complement components: Role of receptors for complement in uptake of zymosan
    • Ezekowitz, A., R. Sim, M. Hill, and S. Gordon. 1983. Local opsonization by secreted macrophage complement components: role of receptors for complement in uptake of zymosan. J. Exp. Med. 159:244-260.
    • (1983) J. Exp. Med. , vol.159 , pp. 244-260
    • Ezekowitz, A.1    Sim, R.2    Hill, M.3    Gordon, S.4
  • 24
    • 0027155908 scopus 로고
    • Phospholipase D activity in phagocytic leukocytes is synergistically regulated by G-protein- and tyrosine kinase-based mechanisms
    • Dubyak, G.R., S.J. Schomisch, D.J. Kusner, and M. Xie. 1993. Phospholipase D activity in phagocytic leukocytes is synergistically regulated by G-protein- and tyrosine kinase-based mechanisms. Biochem. J. 292:121-128.
    • (1993) Biochem. J. , vol.292 , pp. 121-128
    • Dubyak, G.R.1    Schomisch, S.J.2    Kusner, D.J.3    Xie, M.4
  • 25
    • 0027317034 scopus 로고
    • ATP-induced potentiation of G-protein-dependent phospholipase D activity in a cell-free system from U937 promonocytic leukocytes
    • Kusner, D.J., S.J. Schomisch, and G.R. Dubyak. 1993. ATP-induced potentiation of G-protein-dependent phospholipase D activity in a cell-free system from U937 promonocytic leukocytes. J. Biol. Chem. 268:19973-19982.
    • (1993) J. Biol. Chem. , vol.268 , pp. 19973-19982
    • Kusner, D.J.1    Schomisch, S.J.2    Dubyak, G.R.3
  • 27
    • 0001912380 scopus 로고
    • Regression and correlation
    • Little, Brown and Co., Boston
    • Colton, T. 1974. Regression and correlation. In Statistics in Medicine. Little, Brown and Co., Boston. 189-218.
    • (1974) Statistics in Medicine , pp. 189-218
    • Colton, T.1
  • 28
    • 0027160443 scopus 로고
    • The phosphatase inhibitor 2,3-diphosphoglycerate interferes with phospholipase D activation in rabbit neutrophils
    • Kanaho, Y., Y. Nakai, M. Katoh, and Y. Nozawa. 1993. The phosphatase inhibitor 2,3-diphosphoglycerate interferes with phospholipase D activation in rabbit neutrophils. J. Biol. Chem. 268:12492-12497.
    • (1993) J. Biol. Chem. , vol.268 , pp. 12492-12497
    • Kanaho, Y.1    Nakai, Y.2    Katoh, M.3    Nozawa, Y.4
  • 29
    • 0027057976 scopus 로고
    • Phospholipase D mimics platelet-derived growth factor as a competence factor in vascular smooth muscle cells
    • Kondo, T., H. Inui, F. Konishi, and T. Inagami. 1992. Phospholipase D mimics platelet-derived growth factor as a competence factor in vascular smooth muscle cells. J. Biol. Chem. 267:23609-23616.
    • (1992) J. Biol. Chem. , vol.267 , pp. 23609-23616
    • Kondo, T.1    Inui, H.2    Konishi, F.3    Inagami, T.4
  • 30
    • 0026725673 scopus 로고
    • Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal
    • Fukami, K., and T. Takenawa. 1992. Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal. J. Biol. Chem. 267:10988-10993.
    • (1992) J. Biol. Chem. , vol.267 , pp. 10988-10993
    • Fukami, K.1    Takenawa, T.2
  • 31
    • 0025812838 scopus 로고
    • Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes
    • Agwu, D.E., L.C. McPhail, S. Sozzani, D.A. Bass, and C.E. McCall. 1991. Phosphatidic acid as a second messenger in human polymorphonuclear leukocytes. J. Clin. Invest. 88:531-539.
    • (1991) J. Clin. Invest. , vol.88 , pp. 531-539
    • Agwu, D.E.1    McPhail, L.C.2    Sozzani, S.3    Bass, D.A.4    McCall, C.E.5
  • 32
    • 0026710617 scopus 로고
    • Peroxides of vanadate induce activation of phospholipase D in HL-60 cells
    • Bourgoin, S., and S. Grinstein. 1992. Peroxides of vanadate induce activation of phospholipase D in HL-60 cells. J. Biol. Chem. 267:11908-11916.
    • (1992) J. Biol. Chem. , vol.267 , pp. 11908-11916
    • Bourgoin, S.1    Grinstein, S.2
  • 33
    • 0026541691 scopus 로고
    • Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil
    • Uings, I.J., N.T. Thompson, R.W. Randall, G.D. Spacey, R.W. Bonser, A.T. Hudson, and L.G. Garland. 1992. Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil. Biochem. J. 281:597-600.
    • (1992) Biochem. J. , vol.281 , pp. 597-600
    • Uings, I.J.1    Thompson, N.T.2    Randall, R.W.3    Spacey, G.D.4    Bonser, R.W.5    Hudson, A.T.6    Garland, L.G.7
  • 34
    • 0028167979 scopus 로고
    • β2 integrin-dependent protein tyrosine phosphorylation and activation of the FdR protein tyrosine kinase in human neutrophils
    • Berton, G., L. Fumagalli, C. Laudanna, and C. Sorio. 1994. β2 integrin-dependent protein tyrosine phosphorylation and activation of the FdR protein tyrosine kinase in human neutrophils. J. Cell Biol. 126:1111-1121.
    • (1994) J. Cell Biol. , vol.126 , pp. 1111-1121
    • Berton, G.1    Fumagalli, L.2    Laudanna, C.3    Sorio, C.4
  • 35
    • 0028170990 scopus 로고
    • β2 integrin-dependent tyrosine phosphorylation of paxillin in human neutrophils treated with tumor necrosis factor
    • Fuortes, M., W.-W. Jin, and C. Nathan. 1994. β2 integrin-dependent tyrosine phosphorylation of paxillin in human neutrophils treated with tumor necrosis factor. J. Cell Biol. 127:1477-1483.
    • (1994) J. Cell Biol. , vol.127 , pp. 1477-1483
    • Fuortes, M.1    Jin, W.-W.2    Nathan, C.3
  • 36
    • 0028960755 scopus 로고
    • Zymosan-triggered association of tyrosine phosphoproteins and lyn kinase with cytoskeleton in human monocytes
    • Zaffran, Y., J.C. Escallier, S. Ruta, C. Capo, and J.L. Mege. 1995. Zymosan-triggered association of tyrosine phosphoproteins and lyn kinase with cytoskeleton in human monocytes. J. Immunol. 154:3488-3497.
    • (1995) J. Immunol. , vol.154 , pp. 3488-3497
    • Zaffran, Y.1    Escallier, J.C.2    Ruta, S.3    Capo, C.4    Mege, J.L.5
  • 37
    • 0028145707 scopus 로고
    • Tyrosine phosphorylation of the γ subunit of Fcγ receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis
    • Greenberg, S., P. Chang, and S.C. Silverstein. 1994. Tyrosine phosphorylation of the γ subunit of Fcγ receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis. J. Biol. Chem. 269:3897-3902.
    • (1994) J. Biol. Chem. , vol.269 , pp. 3897-3902
    • Greenberg, S.1    Chang, P.2    Silverstein, S.C.3
  • 38
    • 0029019812 scopus 로고
    • Distinct tyrosine kinase activation and Triton X-100 insolubility upon FcγRII or FcγRIIIB ligation in human polymorphonuclear leukocytes
    • Zhou, M., D.M. Lublin, D.C. Link, and E.J. Brown. 1995. Distinct tyrosine kinase activation and Triton X-100 insolubility upon FcγRII or FcγRIIIB ligation in human polymorphonuclear leukocytes. J. Biol. Chem. 270:13553-13560.
    • (1995) J. Biol. Chem. , vol.270 , pp. 13553-13560
    • Zhou, M.1    Lublin, D.M.2    Link, D.C.3    Brown, E.J.4
  • 40
    • 0029008487 scopus 로고
    • Herbimycin A: Induces the 20S proteosome- and ubiquitin-dependent degradation of receptor tyrosine kinases
    • Sepp-Lorenzino, L., Z. Ma, D.E. Lebwohl, A. Vinitsky, and N. Rosen. 1995. Herbimycin A: induces the 20S proteosome- and ubiquitin-dependent degradation of receptor tyrosine kinases. J. Biol. Chem. 270:16580-16587.
    • (1995) J. Biol. Chem. , vol.270 , pp. 16580-16587
    • Sepp-Lorenzino, L.1    Ma, Z.2    Lebwohl, D.E.3    Vinitsky, A.4    Rosen, N.5
  • 42
    • 0025608606 scopus 로고
    • Molecular characterization of the human macrophage mannose receptor: Demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells
    • Ezekowitz, R.A.B., K. Sastry, P. Bailly, and A. Warner. 1990. Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells. J. Exp. Med. 172:1785-1794.
    • (1990) J. Exp. Med. , vol.172 , pp. 1785-1794
    • Ezekowitz, R.A.B.1    Sastry, K.2    Bailly, P.3    Warner, A.4
  • 43
    • 0022494854 scopus 로고
    • Natural mycobacteriostatic activity in human monocyte-derived adherent cells
    • Douvas, G.S., E.M. Berger, J.E. Repine, and A.J. Crowle. 1986. Natural mycobacteriostatic activity in human monocyte-derived adherent cells. Am. Rev. Respir. Dis. 134:44-18.
    • (1986) Am. Rev. Respir. Dis. , vol.134 , pp. 44-118
    • Douvas, G.S.1    Berger, E.M.2    Repine, J.E.3    Crowle, A.J.4
  • 44
    • 0027495890 scopus 로고
    • The regulation of phospholipase C-γ1 by phosphatidic acid
    • Jones, G.A., and G. Carpenter. 1993. The regulation of phospholipase C-γ1 by phosphatidic acid. J. Biol. Chem. 268: 20845-20850.
    • (1993) J. Biol. Chem. , vol.268 , pp. 20845-20850
    • Jones, G.A.1    Carpenter, G.2
  • 45
    • 0029096185 scopus 로고
    • Cell-free activation of neutrophil NADPH oxidase by a phosphatidic acid-regulated protein kinase
    • McPhail, L.C., D. Qualliotine-Mann, and K.A. Waite. 1995. Cell-free activation of neutrophil NADPH oxidase by a phosphatidic acid-regulated protein kinase. Proc. Natl. Acad. Sci. USA. 92:7931-7935.
    • (1995) Proc. Natl. Acad. Sci. USA , vol.92 , pp. 7931-7935
    • McPhail, L.C.1    Qualliotine-Mann, D.2    Waite, K.A.3
  • 46
    • 0025807146 scopus 로고
    • 2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic difterentiation of HL-60 cells
    • 2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic difterentiation of HL-60 cells. J. Clin. Invest. 88:45-54.
    • (1991) J. Clin. Invest. , vol.88 , pp. 45-54
    • Xie, M.1    Jacobs, L.S.2    Dubyak, G.R.3


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