IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments

Journal of Neuroinflammation

Robert Zorec³  Milos Pekny²  Maryam Faiz²  Yolanda de Pablo²  Matjaž Jeras⁵  Marko Kreft¹  Urban Švajger⁴  Maja Potokar³  Mateja Gabrijel³  Nina Vardjan³ 

[1] Biotechnical Faculty, University of Ljubljana, Večna pot 111, Ljubljana 1000, Slovenia;Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Medicinaregatan 9A, Gothenburg, 413 90, Sweden;Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, Ljubljana 1000, Slovenia;Blood Transfusion Center of Slovenia, Šlajmerjeva 6, Ljubljana 1000, Slovenia;Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 5, Ljubljana 1000, Slovenia

关键词: Immune response;    Dextran labeling;    Interferon-γ;    Major histocompatibility class II compartments;    Late endosomes/lysosomes;    Vesicle mobility;    Astrocytes;   

Others  :  1212486
DOI  :  10.1186/1742-2094-9-144

 received in 2012-04-07, accepted in 2012-05-28,  发布年份 2012

【 摘 要 】

Background

In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs.

Methods

The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor⁵⁴⁶-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software.

Results

Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor⁵⁴⁶-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent.

Conclusions

Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.

【 授权许可】

   
2012 Vardjan et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Berger AC, Roche PA: MHC class II transport at a glance. J Cell Sci 2009, 122:1-4.
• [2]Cresswell P: Antigen processing and presentation. Immunol Rev 2005, 207:5-7.
• [3]Shrikant P, Benveniste EN: The central nervous system as an immunocompetent organ: role of glial cells in antigen presentation. J Immunol 1996, 157:1819-1822.
• [4]Hirsch MR, Wietzerbin J, Pierres M, Goridis C: Expression of Ia antigens by cultured astrocytes treated with gamma-interferon. Neurosci Lett 1983, 41:199-204.
• [5]Fontana A, Fierz W, Wekerle H: Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 1984, 307:273-276.
• [6]Soos JM, Morrow J, Ashley TA, Szente BE, Bikoff EK, Zamvil SS: Astrocytes express elements of the class II endocytic pathway and process central nervous system autoantigen for presentation to encephalitogenic T cells. J Immunol 1998, 161:5959-5966.
• [7]Lee SC, Collins M, Vanguri P, Shin ML: Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J Immunol 1992, 148:3391-3397.
• [8]Neumann H: Control of glial immune function by neurons. Glia 2001, 36:191-199.
• [9]Nikcevich KM, Gordon KB, Tan L, Hurst SD, Kroepfl JF, Gardinier M, Barrett TA, Miller SD: IFN-gamma-activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells. J Immunol 1997, 158:614-621.
• [10]Zeinstra E, Wilczak N, Chesik D, Glazenburg L, Kroese FG, De Keyser J: Simvastatin inhibits interferon-gamma-induced MHC class II up-regulation in cultured astrocytes. J Neuroinflammation 2006, 3:16. BioMed Central Full Text
• [11]Barois N, Forquet F, Davoust J: Actin microfilaments control the MHC class II antigen presentation pathway in B cells. J Cell Sci 1998, 111:1791-1800.
• [12]Vascotto F, Lankar D, Faure-André G, Vargas P, Diaz J, Le Roux D, Yuseff MI, Sibarita JB, Boes M, Raposo G, Mougneau E, Glaichenhaus N, Bonnerot C, Manoury B, Lennon-Dumenil AM: The actin-based motor protein myosin II regulates MHC class II trafficking and BCR-driven antigen presentation. J Cell Biol 2007, 176:1007-1019.
• [13]Wubbolts R, Fernandez-Borja M, Jordens I, Reits E, Dusseljee S, Echeverri C, Vallee RB, Neefjes J: Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments. J Cell Sci 1999, 112:785-795.
• [14]Vyas JM, Kim YM, Artavanis-Tsakonas K, Love JC, Van der Veen AG, Ploegh HL: Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells. J Immunol 2007, 178:7199-7210.
• [15]Kim S, Coulombe PA: Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Genes Dev 2007, 21:1581-1597.
• [16]Pekny M, Pekna M: Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol 2004, 204:428-437.
• [17]Pekny M, Nilsson M: Astrocyte activation and reactive gliosis. Glia 2005, 50:427-434.
• [18]Eliasson C, Sahlgren C, Berthold C, Stakeberg J, Celis J, Betsholtz C, Eriksson J, Pekny M: Intermediate filament protein partnership in astrocytes. J Biol Chem 1999, 274:23996-24006.
• [19]Potokar M, Kreft M, Li L, Daniel Andersson J, Pangrsic T, Chowdhury H, Pekny M, Zorec R: Cytoskeleton and vesicle mobility in astrocytes. Traffic 2007, 8:12-20.
• [20]Potokar M, Stenovec M, Gabrijel M, Li L, Kreft M, Grilc S, Pekny M, Zorec R: Intermediate filaments attenuate stimulation-dependent mobility of endosomes/lysosomes in astrocytes. Glia 2010, 58:1208-1219.
• [21]Schwartz J, Wilson D: Preparation and characterization of type 1 astrocytes cultured from adult rat cortex, cerebellum, and striatum. Glia 1992, 5:75-80.
• [22]Pekny M, Levéen P, Pekna M, Eliasson C, Berthold C, Westermark B, Betsholtz C: Mice lacking glial fibrillary acidic protein display astrocytes devoid of intermediate filaments but develop and reproduce normally. EMBO J 1995, 14:1590-1598.
• [23]Potokar M, Kreft M, Pangrsic T, Zorec R: Vesicle mobility studied in cultured astrocytes. Biochem Biophys Res Commun 2005, 329:678-683.
• [24]Pekny M, Johansson C, Eliasson C, Stakeberg J, Wallén A, Perlmann T, Lendahl U, Betsholtz C, Berthold C, Frisén J: Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol 1999, 145:503-514.
• [25]Colucci-Guyon E, Portier M, Dunia I, Paulin D, Pournin S, Babinet C: Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 1994, 79:679-694.
• [26]Bunbury A, Potolicchio I, Maitra R, Santambrogio L: Functional analysis of monocyte MHC class II compartments. FASEB J 2009, 23:164-171.
• [27]van Niel G, Wubbolts R, Stoorvogel W: Endosomal sorting of MHC class II determines antigen presentation by dendritic cells. Curr Opin Cell Biol 2008, 20:437-444.
• [28]Jaiswal JK, Andrews NW, Simon SM: Membrane proximal lysosomes are the major vesicles responsible for calcium-dependent exocytosis in nonsecretory cells. J Cell Biol 2002, 159:625-635.
• [29]Gabrijel M, Kreft M, Zorec R: Monitoring lysosomal fusion in electrofused hybridoma cells. Biochim Biophys Acta 2008, 1778:483-490.
• [30]Jaiswal JK, Fix M, Takano T, Nedergaard M, Simon SM: Resolving vesicle fusion from lysis to monitor calcium-triggered lysosomal exocytosis in astrocytes. Proc Natl Acad Sci U S A 2007, 104:14151-14156.
• [31]Li D, Ropert N, Koulakoff A, Giaume C, Oheim M: Lysosomes are the major vesicular compartment undergoing Ca2 + -regulated exocytosis from cortical astrocytes. J Neurosci 2008, 28:7648-7658.
• [32]Jiang M, Chen G: Ca2+ regulation of dynamin-independent endocytosis in cortical astrocytes. J Neurosci 2009, 29:8063-8074.
• [33]Bennett MR, Farnell L, Gibson WG: A quantitative model of purinergic junctional transmission of calcium waves in astrocyte networks. Biophys J 2005, 89:2235-2250.
• [34]Stenovec M, Kreft M, Grilc S, Potokar M, Kreft M, Pangrsic T, Zorec R: Ca2+-dependent mobility of vesicles capturing anti-VGLUT1 antibodies. Exp Cell Res 2007, 313:3809-3818.
• [35]Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Ståhlberg A, Aprico K, Larsson K, Yabe T, Moons L, Fotheringham A, Davies I, Carmeliet P, Schwartz JP, Pekna M, Kubista M, Blomstrand F, Maragakis N, Nilsson M, Pekny M: Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 2008, 28:468-481.
• [36]Nieminen M, Henttinen T, Merinen M, Marttila-Ichihara F, Eriksson JE, Jalkanen S: Vimentin function in lymphocyte adhesion and transcellular migration. Nat Cell Biol 2006, 8:156-162.
• [37]Perlson E, Hanz S, Ben-Yaakov K, Segal-Ruder Y, Seger R, Fainzilber M: Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve. Neuron 2005, 45:715-726.
• [38]Styers ML, Salazar G, Love R, Peden AA, Kowalczyk AP, Faundez V: The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton. Mol Biol Cell 2004, 15:5369-5382.
• [39]Wagner OI, Lifshitz J, Janmey PA, Linden M, McIntosh TK, Leterrier JF: Mechanisms of mitochondria-neurofilament interactions. J Neurosci 2003, 23:9046-9058.
• [40]Gao YS, Vrielink A, MacKenzie R, Sztul E: A novel type of regulation of the vimentin intermediate filament cytoskeleton by a Golgi protein. Eur J Cell Biol 2002, 81:391-401.
• [41]Chang L, Barlan K, Chou YH, Grin B, Lakonishok M, Serpinskaya AS, Shumaker DK, Herrmann H, Gelfand VI, Goldman RD: The dynamic properties of intermediate filaments during organelle transport. J Cell Sci 2009, 122:2914-2923.
• [42]Stenovec M, Milošević M, Petrušić V, Potokar M, Stević Z, Prebil M, Kreft M, Trkov S, Andjus PR, Zorec R: Amyotrophic lateral sclerosis immunoglobulins G enhance the mobility of Lysotracker-labelled vesicles in cultured rat astrocytes. Acta Physiol (Oxf) 2011, 203:457-471.
• [43]Chow A, Toomre D, Garrett W, Mellman I: Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 2002, 418:988-994.
• [44]Boes M, Cerny J, Massol R, Op den Brouw M, Kirchhausen T, Chen J, Ploegh HL: T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature 2002, 418:983-988.
• [45]Helfand BT, Chang L, Goldman RD: Intermediate filaments are dynamic and motile elements of cellular architecture. J Cell Sci 2004, 117:133-141.
• [46]Chang L, Goldman RD: Intermediate filaments mediate cytoskeletal crosstalk. Nat Rev Mol Cell Biol 2004, 5:601-613.
• [47]Junyent F, De Lemos L, Utrera J, Paco S, Aguado F, Camins A, Pallàs M, Romero R, Auladell C: Content and traffic of taurine in hippocampal reactive astrocytes. Hippocampus 2011, 21:185-197.
• [48]Wubbolts R, Fernandez-Borja M, Oomen L, Verwoerd D, Janssen H, Calafat J, Tulp A, Dusseljee S, Neefjes J: Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface. J Cell Biol 1996, 135:611-622.
• [49]Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, Wang W, Gu XS, Duan S: Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 2007, 9:945-953.
• [50]Vardjan N, Stenovec M, Jorgacevski J, Kreft M, Zorec R: Subnanometer fusion pores in spontaneous exocytosis of peptidergic vesicles. J Neurosci 2007, 27:4737-4746.
• [51]Harata N, Aravanis A, Tsien R: Kiss-and-run and full-collapse fusion as modes of exo-endocytosis in neurosecretion. J Neurochem 2006, 97:1546-1570.
• [52]Luzio JP, Pryor PR, Bright NA: Lysosomes: fusion and function. Nat Rev Mol Cell Biol 2007, 8:622-632.
• [53]Potokar M, Stenovec M, Kreft M, Kreft M, Zorec R: Stimulation inhibits the mobility of recycling peptidergic vesicles in astrocytes. Glia 2008, 56:135-144.