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Published in: Arthritis Research & Therapy 4/2006

Open Access 01-08-2006 | Research article

Inhibition of macropinocytosis blocks antigen presentation of type II collagen in vitro and in vivoin HLA-DR1 transgenic mice

Authors: Alexei von Delwig, Catharien MU Hilkens, Daniel M Altmann, Rikard Holmdahl, John D Isaacs, Clifford V Harding, Helen Robertson, Norman McKie, John H Robinson

Published in: Arthritis Research & Therapy | Issue 4/2006

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Abstract

Professional antigen-presenting cells, such as dendritic cells, macrophages and B cells have been implicated in the pathogenesis of rheumatoid arthritis, constituting a possible target for antigen-specific immunotherapy. We addressed the possibility of blocking antigen presentation of the type II collagen (CII)-derived immunodominant arthritogenic epitope CII259–273 to specific CD4 T cells by inhibition of antigen uptake in HLA-DR1-transgenic mice in vitro and in vivo. Electron microscopy, confocal microscopy, subcellular fractionation and antigen presentation assays were used to establish the mechanisms of uptake, intracellular localization and antigen presentation of CII by dendritic cells and macrophages. We show that CII accumulated in membrane fractions of intermediate density corresponding to late endosomes. Treatment of dendritic cells and macrophages with cytochalasin D or amiloride prevented the intracellular appearance of CII and blocked antigen presentation of CII259–273 to HLA-DR1-restricted T cell hybridomas. The data suggest that CII was taken up by dendritic cells and macrophages predominantly via macropinocytosis. Administration of amiloride in vivo prevented activation of CII-specific polyclonal T cells in the draining popliteal lymph nodes. This study suggests that selective targeting of CII internalization in professional antigen-presenting cells prevents activation of autoimmune T cells, constituting a novel therapeutic strategy for the immunotherapy of rheumatoid arthritis.
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Literature
1.
go back to reference Bayry J, Thirion M, Delignat S, Misra N, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV: Dendritic cells and autoimmunity. Autoimmun Rev. 2004, 3: 183-187.CrossRefPubMed Bayry J, Thirion M, Delignat S, Misra N, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV: Dendritic cells and autoimmunity. Autoimmun Rev. 2004, 3: 183-187.CrossRefPubMed
2.
go back to reference Holmdahl R, Tarkowski A, Jonsson R: Involvement of macrophages and dendritic cells in synovial inflammation of collagen induced arthritis in DBA/1 mice and spontaneous arthritis in MRL/lpr mice. Autoimmunity. 1991, 8: 271-280.CrossRefPubMed Holmdahl R, Tarkowski A, Jonsson R: Involvement of macrophages and dendritic cells in synovial inflammation of collagen induced arthritis in DBA/1 mice and spontaneous arthritis in MRL/lpr mice. Autoimmunity. 1991, 8: 271-280.CrossRefPubMed
3.
go back to reference Panayi GS: B cells: a fundamental role in the pathogenesis of rheumatoid arthritis?. Rheumatology (Oxford). 2005, 44: 3-7.CrossRef Panayi GS: B cells: a fundamental role in the pathogenesis of rheumatoid arthritis?. Rheumatology (Oxford). 2005, 44: 3-7.CrossRef
4.
go back to reference Ludewig B, Junt T, Hengartner H, Zinkernagel RM: Dendritic cells in autoimmune diseases. Curr Opin Immunol. 2001, 13: 657-662.CrossRefPubMed Ludewig B, Junt T, Hengartner H, Zinkernagel RM: Dendritic cells in autoimmune diseases. Curr Opin Immunol. 2001, 13: 657-662.CrossRefPubMed
5.
go back to reference Dittel BN, Visintin I, Merchant RM, Janeway CAJ: Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis. J Immunol. 1999, 163: 32-39.PubMed Dittel BN, Visintin I, Merchant RM, Janeway CAJ: Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis. J Immunol. 1999, 163: 32-39.PubMed
6.
go back to reference Leung BP, Conacher M, Hunter D, McInnes IB, Liew FY, Brewer JM: A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation. J Immunol. 2002, 169: 7071-7077.CrossRefPubMed Leung BP, Conacher M, Hunter D, McInnes IB, Liew FY, Brewer JM: A novel dendritic cell-induced model of erosive inflammatory arthritis: distinct roles for dendritic cells in T cell activation and induction of local inflammation. J Immunol. 2002, 169: 7071-7077.CrossRefPubMed
7.
8.
go back to reference Pettit AR, Thomas R: Dendritic cells: the driving force behind autoimmunity in rheumatoid arthritis?. Immunol Cell Biol. 1999, 77: 420-427.CrossRefPubMed Pettit AR, Thomas R: Dendritic cells: the driving force behind autoimmunity in rheumatoid arthritis?. Immunol Cell Biol. 1999, 77: 420-427.CrossRefPubMed
9.
go back to reference Del Nagro CJ, Kolla RV, Rickert RC: A critical role for complement C3d and the B cell coreceptor (CD19/CD21) complex in the initiation of inflammatory arthritis. J Immunol. 2005, 175: 5379-5389.CrossRefPubMed Del Nagro CJ, Kolla RV, Rickert RC: A critical role for complement C3d and the B cell coreceptor (CD19/CD21) complex in the initiation of inflammatory arthritis. J Immunol. 2005, 175: 5379-5389.CrossRefPubMed
10.
go back to reference Holmdahl M, Vestberg M, Holmdahl R: Primed B cells present type-II collagen to T cells. Scand J Immunol. 2002, 55: 382-389.CrossRefPubMed Holmdahl M, Vestberg M, Holmdahl R: Primed B cells present type-II collagen to T cells. Scand J Immunol. 2002, 55: 382-389.CrossRefPubMed
11.
go back to reference O'Neill SK, Shlomchik MJ, Glant TT, Cao Y, Doodes PD, Finnegan A: Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J Immunol. 2005, 174: 3781-3788.CrossRefPubMed O'Neill SK, Shlomchik MJ, Glant TT, Cao Y, Doodes PD, Finnegan A: Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J Immunol. 2005, 174: 3781-3788.CrossRefPubMed
12.
go back to reference Holmdahl M, Grubb A, Holmdahl R: Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells. Int Immunol. 2004, 16: 717-726.CrossRefPubMed Holmdahl M, Grubb A, Holmdahl R: Cysteine proteases in Langerhans cells limits presentation of cartilage derived type II collagen for autoreactive T cells. Int Immunol. 2004, 16: 717-726.CrossRefPubMed
13.
go back to reference Manoury-Schwartz B, Chiocchia G, Lotteau V, Fournier C: Selective increased presentation of type II collagen by leupeptin. Int Immunol. 1997, 9: 581-589.CrossRefPubMed Manoury-Schwartz B, Chiocchia G, Lotteau V, Fournier C: Selective increased presentation of type II collagen by leupeptin. Int Immunol. 1997, 9: 581-589.CrossRefPubMed
14.
go back to reference Cremer MA, Rosloniec EF, Kang AH: The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease. J Mol Med. 1998, 76: 275-288.CrossRefPubMed Cremer MA, Rosloniec EF, Kang AH: The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease. J Mol Med. 1998, 76: 275-288.CrossRefPubMed
15.
go back to reference Brand DD, Kang AH, Rosloniec EF: The mouse model of collagen-induced arthritis. Autoimmunity. Methods and Protocols. 2004, Totowa, NJ: Humana Press, 102: 295-312. Edited by Perl A Brand DD, Kang AH, Rosloniec EF: The mouse model of collagen-induced arthritis. Autoimmunity. Methods and Protocols. 2004, Totowa, NJ: Humana Press, 102: 295-312. Edited by Perl A
16.
go back to reference Kim WU, Cho ML, Yung YO, Min SY, Park SW, Min DJ, Joon JH, Kim HY: Type II collagen autoimmunity in rheumatoid arthritis. Am J Med Sci. 2004, 327: 202-211.CrossRefPubMed Kim WU, Cho ML, Yung YO, Min SY, Park SW, Min DJ, Joon JH, Kim HY: Type II collagen autoimmunity in rheumatoid arthritis. Am J Med Sci. 2004, 327: 202-211.CrossRefPubMed
17.
go back to reference Lu L, Woo J, Rao AS, Li Y, Watkins SC, Qian S, Starzl TE, Demetris AJ, Thomson AW: Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen. J Exp Med. 1994, 179: 1823-1834.CrossRefPubMed Lu L, Woo J, Rao AS, Li Y, Watkins SC, Qian S, Starzl TE, Demetris AJ, Thomson AW: Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony-stimulating factor and their maturational development in the presence of type-1 collagen. J Exp Med. 1994, 179: 1823-1834.CrossRefPubMed
18.
go back to reference Hao HN, Yang SY, Wooley PH: Direct interactions of collagen II and Toll-like receptor depend upon the saccharide residue of collagen II: a potential mechanism for collagen-induced arthritis. Arthritis Rheum. 2005, 52: S477- Hao HN, Yang SY, Wooley PH: Direct interactions of collagen II and Toll-like receptor depend upon the saccharide residue of collagen II: a potential mechanism for collagen-induced arthritis. Arthritis Rheum. 2005, 52: S477-
19.
go back to reference Pribila JT, Itano AA, Mueller KL, Shimizu Y: The α1β1 and αEβ7 integrins define a subset of dendritic cells in peripheral lymph nodes with unique adhesive and antigen uptake properties. J Immunol. 2004, 172: 282-291.CrossRefPubMed Pribila JT, Itano AA, Mueller KL, Shimizu Y: The α1β1 and αEβ7 integrins define a subset of dendritic cells in peripheral lymph nodes with unique adhesive and antigen uptake properties. J Immunol. 2004, 172: 282-291.CrossRefPubMed
20.
go back to reference Cremer MA, Stuart JM, Townes AS, Kang AH: Collagen-induced polyarthritis in rats: a study of native type II collagen for adjuvant activity. J Immunol. 1980, 124: 2912-2918.PubMed Cremer MA, Stuart JM, Townes AS, Kang AH: Collagen-induced polyarthritis in rats: a study of native type II collagen for adjuvant activity. J Immunol. 1980, 124: 2912-2918.PubMed
21.
22.
go back to reference Sansonetti PJ: Phagocytosis of bacterial pathogens: implications in the host response. Semin Immunol. 2001, 13: 381-390.CrossRefPubMed Sansonetti PJ: Phagocytosis of bacterial pathogens: implications in the host response. Semin Immunol. 2001, 13: 381-390.CrossRefPubMed
23.
go back to reference Kaksonen M, Toret CP, Drubin DG: A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell. 2005, 123: 305-320.CrossRefPubMed Kaksonen M, Toret CP, Drubin DG: A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell. 2005, 123: 305-320.CrossRefPubMed
24.
25.
go back to reference Bathori G, Cervenak L, Karadi I: Caveolae-an alternative endocytotic pathway for targeted drug delivery. Crit Rev Ther Drug Carrier Syst. 2004, 21: 67-95.CrossRefPubMed Bathori G, Cervenak L, Karadi I: Caveolae-an alternative endocytotic pathway for targeted drug delivery. Crit Rev Ther Drug Carrier Syst. 2004, 21: 67-95.CrossRefPubMed
26.
go back to reference Holm B, Baquer SM, Holm L, Holmdahl R, Kihlberg J: Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model for rheumatoid arthritis. Bioorg Med Chem. 2003, 11: 3981-3987.CrossRefPubMed Holm B, Baquer SM, Holm L, Holmdahl R, Kihlberg J: Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model for rheumatoid arthritis. Bioorg Med Chem. 2003, 11: 3981-3987.CrossRefPubMed
27.
go back to reference von Delwig A, Altmann DM, Isaacs JD, Harding CV, Holmdahl R, McKie N, Robinson JH: The impact of glycosylation on HLA-DR1 restricted T cell recognition of type II collagen in a mouse model. Arthritis Rheum. 2006, 54: 482-491.CrossRefPubMed von Delwig A, Altmann DM, Isaacs JD, Harding CV, Holmdahl R, McKie N, Robinson JH: The impact of glycosylation on HLA-DR1 restricted T cell recognition of type II collagen in a mouse model. Arthritis Rheum. 2006, 54: 482-491.CrossRefPubMed
28.
go back to reference von Delwig A, Bailey E, Gibbs D, Robinson JH: The route of bacterial uptake by macrophages influences the repertoire of epitopes presented to CD4 T cells. Eur J Immunol. 2002, 32: 3714-3719.CrossRefPubMed von Delwig A, Bailey E, Gibbs D, Robinson JH: The route of bacterial uptake by macrophages influences the repertoire of epitopes presented to CD4 T cells. Eur J Immunol. 2002, 32: 3714-3719.CrossRefPubMed
29.
go back to reference Werling D, Hope JC, Chaplin P, Collins RA, Taylor G, Howard CJ: Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells. J Leukoc Biol. 1999, 66: 50-58.PubMed Werling D, Hope JC, Chaplin P, Collins RA, Taylor G, Howard CJ: Involvement of caveolae in the uptake of respiratory syncytial virus antigen by dendritic cells. J Leukoc Biol. 1999, 66: 50-58.PubMed
30.
go back to reference Delvig AA, Robinson JH, Wetzler LM: Testing meningococcal vaccines for mitogenicity and superantigenicity. Meningococcal vaccines. Methods and protocols. 2001, Totowa, NJ: Humana Press, 66: 199-221. Edited by: Pollard AJ, Maiden MCJCrossRef Delvig AA, Robinson JH, Wetzler LM: Testing meningococcal vaccines for mitogenicity and superantigenicity. Meningococcal vaccines. Methods and protocols. 2001, Totowa, NJ: Humana Press, 66: 199-221. Edited by: Pollard AJ, Maiden MCJCrossRef
31.
go back to reference Lyons JC, Ross BD, Song CW: Enhancement of hyperthermia effect in vivo by amiloride and DIDS. Int J Radiat Oncol Biol Phys. 1993, 25: 95-103.CrossRefPubMed Lyons JC, Ross BD, Song CW: Enhancement of hyperthermia effect in vivo by amiloride and DIDS. Int J Radiat Oncol Biol Phys. 1993, 25: 95-103.CrossRefPubMed
32.
go back to reference von Delwig A, Ramachandra L, Harding CV, Robinson JH: Localization of peptide/MHC class II complexes in macrophages following antigen processing of viable Streptococcus pyogenes. Eur J Immunol. 2003, 33: 2353-2360.CrossRefPubMed von Delwig A, Ramachandra L, Harding CV, Robinson JH: Localization of peptide/MHC class II complexes in macrophages following antigen processing of viable Streptococcus pyogenes. Eur J Immunol. 2003, 33: 2353-2360.CrossRefPubMed
33.
go back to reference von Delwig A, Musson JA, Shim HK, Lee JJ, Walker N, Harding CV, Williamson ED, Robinson JH: Distribution of productive antigen processing activity for MHC class II presentation in macrophages. Scand J Immunol. 2005, 62: 243-250.CrossRefPubMed von Delwig A, Musson JA, Shim HK, Lee JJ, Walker N, Harding CV, Williamson ED, Robinson JH: Distribution of productive antigen processing activity for MHC class II presentation in macrophages. Scand J Immunol. 2005, 62: 243-250.CrossRefPubMed
34.
go back to reference Grassme HU, Ireland RM, van Putten JPM: Gonococcal opacity protein promotes bacterial entry-associated rearrangements of the epithelial cell actin cytoskeleton. Infect Immun. 1996, 64: 1621-1630.PubMedCentralPubMed Grassme HU, Ireland RM, van Putten JPM: Gonococcal opacity protein promotes bacterial entry-associated rearrangements of the epithelial cell actin cytoskeleton. Infect Immun. 1996, 64: 1621-1630.PubMedCentralPubMed
35.
go back to reference West MA, Bretscher MS, Watts C: Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J Cell Biol. 1989, 109: 2731-2739.CrossRefPubMed West MA, Bretscher MS, Watts C: Distinct endocytotic pathways in epidermal growth factor-stimulated human carcinoma A431 cells. J Cell Biol. 1989, 109: 2731-2739.CrossRefPubMed
36.
go back to reference Valentin-Weigand P, Benkel P, Rohde M, Chhatwal GS: Entry and intracellular survival of group B Streptococci in J774 macrophages. Infect Immun. 1996, 64: 2467-2473.PubMed Valentin-Weigand P, Benkel P, Rohde M, Chhatwal GS: Entry and intracellular survival of group B Streptococci in J774 macrophages. Infect Immun. 1996, 64: 2467-2473.PubMed
37.
go back to reference Harris J, Werling D, Hope JC, Taylor G, Howard CJ: Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol. 2002, 23: 158-164.CrossRefPubMed Harris J, Werling D, Hope JC, Taylor G, Howard CJ: Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol. 2002, 23: 158-164.CrossRefPubMed
38.
go back to reference Tsark EC, Wang W, Teng YC, Arkfeld D, Dodge GR, Kovats S: Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J Immunol. 2002, 169: 6625-6633.CrossRefPubMed Tsark EC, Wang W, Teng YC, Arkfeld D, Dodge GR, Kovats S: Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J Immunol. 2002, 169: 6625-6633.CrossRefPubMed
39.
go back to reference Graham JM: Subcellular fractionation and isolation of organelles. Isolation of lysosomes from tissues and cells by differential and density gradient centrifugation. Current Protocols in Cell Biology. Edited by: Bonifacino JS, Dasso M, Hartford JB, Lippincott-Schwartz J, Yamada KM. 2000, New York: John Wiley & Sons, Inc, 1-21. Graham JM: Subcellular fractionation and isolation of organelles. Isolation of lysosomes from tissues and cells by differential and density gradient centrifugation. Current Protocols in Cell Biology. Edited by: Bonifacino JS, Dasso M, Hartford JB, Lippincott-Schwartz J, Yamada KM. 2000, New York: John Wiley & Sons, Inc, 1-21.
40.
go back to reference Peters PJ, Neefjes JJ, Oorschot V, Ploegh HL, Geuze HJ: Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature. 1991, 349: 669-676.CrossRefPubMed Peters PJ, Neefjes JJ, Oorschot V, Ploegh HL, Geuze HJ: Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature. 1991, 349: 669-676.CrossRefPubMed
41.
go back to reference Jordens I, Marsman M, Kuijl C, Neefjes JJ: Rab proteins, connecting transport and vesicle fusion. Traffic. 2005, 6: 1070-1077.CrossRefPubMed Jordens I, Marsman M, Kuijl C, Neefjes JJ: Rab proteins, connecting transport and vesicle fusion. Traffic. 2005, 6: 1070-1077.CrossRefPubMed
42.
go back to reference Bertram EM, Hawley RG, Watts TH: Overexpression of rab7 enhances the kinetics of antigen processing and presentation with MHC class II molecules in B cells. Int Immunol. 2002, 14: 309-318.CrossRefPubMed Bertram EM, Hawley RG, Watts TH: Overexpression of rab7 enhances the kinetics of antigen processing and presentation with MHC class II molecules in B cells. Int Immunol. 2002, 14: 309-318.CrossRefPubMed
43.
44.
go back to reference Kim HY, Kim WU, Cho ML, Lee SK, Joun J, Kim SI, Yoo WH, Park JH, Min JK, Lee SH, Park SH, Cho CS: Enhanced T cell proliferative response to type II collagen and synthetic peptide CII (255–274) in patients with rheumatoid arthritis. Arthritis Rheum. 1999, 42: 2085-2093.CrossRefPubMed Kim HY, Kim WU, Cho ML, Lee SK, Joun J, Kim SI, Yoo WH, Park JH, Min JK, Lee SH, Park SH, Cho CS: Enhanced T cell proliferative response to type II collagen and synthetic peptide CII (255–274) in patients with rheumatoid arthritis. Arthritis Rheum. 1999, 42: 2085-2093.CrossRefPubMed
45.
go back to reference Bäcklund J, Carlsen S, Hoger T, Holm B, Fugger L, Kihlberg J, Burkhardt H, Holmdahl R: Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis. Proc Natl Acad Sci USA. 2002, 99: 9960-9965.PubMedCentralCrossRefPubMed Bäcklund J, Carlsen S, Hoger T, Holm B, Fugger L, Kihlberg J, Burkhardt H, Holmdahl R: Predominant selection of T cells specific for the glycosylated collagen type II epitope (263–270) in humanized transgenic mice and in rheumatoid arthritis. Proc Natl Acad Sci USA. 2002, 99: 9960-9965.PubMedCentralCrossRefPubMed
46.
go back to reference Haddad JJ: Amiloride and the regulation of NF-κB: an unsung crosstalk and missing link between fluid dynamics and oxidative stress-related inflammation – controversy or pseudo-controversy?. Biochem Biophys Res Commun. 2005, 327: 373-381.CrossRefPubMed Haddad JJ: Amiloride and the regulation of NF-κB: an unsung crosstalk and missing link between fluid dynamics and oxidative stress-related inflammation – controversy or pseudo-controversy?. Biochem Biophys Res Commun. 2005, 327: 373-381.CrossRefPubMed
47.
go back to reference Cuschleri J, Gourlay D, Garcia I, Jelacic S, Maier RV: Endotoxin-induced endothelial cell proinflammatory phenotypic differentiation requires stress fiber polymerization. Shock. 2003, 19: 433-439.CrossRefPubMed Cuschleri J, Gourlay D, Garcia I, Jelacic S, Maier RV: Endotoxin-induced endothelial cell proinflammatory phenotypic differentiation requires stress fiber polymerization. Shock. 2003, 19: 433-439.CrossRefPubMed
48.
go back to reference Everts V, van der Zee E, Creemers LB, Beersten W: Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. Histochem J. 1996, 28: 229-245.CrossRefPubMed Everts V, van der Zee E, Creemers LB, Beersten W: Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. Histochem J. 1996, 28: 229-245.CrossRefPubMed
50.
go back to reference Inaba K, Inaba M: Antigen recognition and presentation by dendritic cells. Int J Hematol. 2005, 81: 181-187.CrossRefPubMed Inaba K, Inaba M: Antigen recognition and presentation by dendritic cells. Int J Hematol. 2005, 81: 181-187.CrossRefPubMed
51.
go back to reference Sallusto F, Cella M, Danieli C, Lanzavecchia A: Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995, 182: 389-400.CrossRefPubMed Sallusto F, Cella M, Danieli C, Lanzavecchia A: Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995, 182: 389-400.CrossRefPubMed
52.
go back to reference Tang CM, Presser F, Morad M: Amiloride selectively blocks the low threshold (T) calcium channel. Science. 1988, 240: 213-215.CrossRefPubMed Tang CM, Presser F, Morad M: Amiloride selectively blocks the low threshold (T) calcium channel. Science. 1988, 240: 213-215.CrossRefPubMed
53.
go back to reference Lai ZF, Chen YZ, Nishimura Y, Nishi K: An amiloride-sensitive and voltage-dependent Na+ channel in an HLA-DR-restricted human T cell clone. J Immunol. 2000, 165: 83-90.CrossRefPubMed Lai ZF, Chen YZ, Nishimura Y, Nishi K: An amiloride-sensitive and voltage-dependent Na+ channel in an HLA-DR-restricted human T cell clone. J Immunol. 2000, 165: 83-90.CrossRefPubMed
54.
go back to reference Dyer KD, Linz-Mcgillem LA, Alliegro MA, Alliegro MC: Receptor-bound uPA is reversibly protected from inhibition by low molecular weight inhibitors. Cell Biol Int. 2002, 26: 327-335.CrossRefPubMed Dyer KD, Linz-Mcgillem LA, Alliegro MA, Alliegro MC: Receptor-bound uPA is reversibly protected from inhibition by low molecular weight inhibitors. Cell Biol Int. 2002, 26: 327-335.CrossRefPubMed
55.
go back to reference Liossis SN, Sfikakis PP: Costimulation blockade in the treatment of rheumatic diseases. BioDrugs. 2004, 18: 95-102.CrossRefPubMed Liossis SN, Sfikakis PP: Costimulation blockade in the treatment of rheumatic diseases. BioDrugs. 2004, 18: 95-102.CrossRefPubMed
56.
go back to reference Falcioni F, Ito K, Vidovic D, Belunis C, Campbell R, Berthel SJ, Bolin DR, Gillespie PB, Huby N, Olson GL, et al: Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules. Nat Biotechnol. 1999, 17: 562-567.CrossRefPubMed Falcioni F, Ito K, Vidovic D, Belunis C, Campbell R, Berthel SJ, Bolin DR, Gillespie PB, Huby N, Olson GL, et al: Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules. Nat Biotechnol. 1999, 17: 562-567.CrossRefPubMed
57.
go back to reference Zeyda M, Poglitsch M, Geyeregger R, Smolen JS, Zlabinger GJ, Hörl WH, Waldhäusl W, Stulnig TM, Säemann MD: Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation. Arthritis Rheum. 2005, 52: 2730-2739.CrossRefPubMed Zeyda M, Poglitsch M, Geyeregger R, Smolen JS, Zlabinger GJ, Hörl WH, Waldhäusl W, Stulnig TM, Säemann MD: Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation. Arthritis Rheum. 2005, 52: 2730-2739.CrossRefPubMed
Metadata
Title
Inhibition of macropinocytosis blocks antigen presentation of type II collagen in vitro and in vivoin HLA-DR1 transgenic mice
Authors
Alexei von Delwig
Catharien MU Hilkens
Daniel M Altmann
Rikard Holmdahl
John D Isaacs
Clifford V Harding
Helen Robertson
Norman McKie
John H Robinson
Publication date
01-08-2006
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2006
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar1964

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