publication . Article . Other literature type . 2019

Clostridium perfringens epsilon toxin induces blood brain barrier permeability via caveolae-dependent transcytosis and requires expression of MAL.

Timothy Vartanian; Jennifer R. Linden; Eric F. Schmidt; Marissa Valenzuela; Francisco A. Uzal; Claudia Flores; Adam O Michel; Sebastian Dobrow;
Open Access English
  • Published: 08 Nov 2019 Journal: PLoS Pathogens, volume 15, issue 11 (issn: 1553-7366, eissn: 1553-7374, Copyright policy)
  • Publisher: Public Library of Science
  • Country: United States
Abstract
Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, in...
Subjects
free text keywords: Research Article, Research and Analysis Methods, Bioassays and Physiological Analysis, Cardiovascular Analysis, Blood-Brain Barrier Permeability Assay, Biology and Life Sciences, Anatomy, Nervous System, Central Nervous System, Medicine and Health Sciences, Cell Biology, Cellular Structures and Organelles, Cell Membranes, Coated Pits, Cellular Types, Animal Cells, Epithelial Cells, Endothelial Cells, Biological Tissue, Epithelium, Vesicles, Endosomes, Cell Processes, Cell Death, Imaging Techniques, Fluorescence Imaging, Toxicology, Toxic Agents, Toxins, Pathology and Laboratory Medicine, Immunology, Genetics, Molecular Biology, Microbiology, Parasitology, Virology, Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5, Blood-Brain Barrier, Brain, Animals, Mice, Inbred C57BL, Knockout, Bacterial Toxins, Cell Membrane Permeability, Caveolin 1, Myelin and Lymphocyte-Associated Proteolipid Proteins, Medical Microbiology, EEA1, Chemistry, Dynamin, Transcytosis, Endosome, Caveolae, Blood–brain barrier, medicine.anatomical_structure, medicine, Internalization, media_common.quotation_subject, media_common, Extravasation
Funded by
NIH| Profiling axonal RNA in vivo using a viral TRAP approach.
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R21NS105047-01A1
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Molecular phenotyping of cortical cell types in multiple rodent models of ALS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01NS091722-03
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Communities
Neuroinformatics
120 references, page 1 of 8

1 Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178–201. 10.1016/j.neuron.2008.01.003 .18215617 [OpenAIRE] [PubMed] [DOI]

2 Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol. 2006;1(3):223–36. 10.1007/s11481-006-9025-3 .18040800 [OpenAIRE] [PubMed] [DOI]

3 Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85. 10.1124/pr.57.2.4 .15914466 [OpenAIRE] [PubMed] [DOI]

4 Engelhardt B. Development of the blood-brain barrier. Cell Tissue Res. 2003;314(1):119–29. 10.1007/s00441-003-0751-z .12955493 [OpenAIRE] [PubMed] [DOI]

5 Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res. 1998;53(6):637–44. 10.1002/(SICI)1097-4547(19980915)53:6<637::AID-JNR1>3.0.CO;2-6 .9753191 [OpenAIRE] [PubMed] [DOI]

6 Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia. 2013;61(12):1939–58. 10.1002/glia.22575 .24123158 [OpenAIRE] [PubMed] [DOI]

7 Abbott NJ, Friedman A. Overview and introduction: the blood-brain barrier in health and disease. Epilepsia. 2012;53 Suppl 6:1–6. 10.1111/j.1528-1167.2012.03696.x .23134489 [OpenAIRE] [PubMed] [DOI]

8 Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7(1):41–53. 10.1038/nrn1824 .16371949 [OpenAIRE] [PubMed] [DOI]

9 Gloor SM, Wachtel M, Bolliger MF, Ishihara H, Landmann R, Frei K. Molecular and cellular permeability control at the blood-brain barrier. Brain Res Brain Res Rev. 2001;36(2–3):258–64. 10.1016/s0165-0173(01)00102-3 .11690623 [OpenAIRE] [PubMed] [DOI]

10 Tietz S, Engelhardt B. Brain barriers: Crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209(4):493–506. 10.1083/jcb.201412147 .26008742 [OpenAIRE] [PubMed] [DOI]

11 Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol. 2002;38(6):323–37. .12529927 [OpenAIRE] [PubMed]

12 De Bock M, Van Haver V, Vandenbroucke RE, Decrock E, Wang N, Leybaert L. Into rather unexplored terrain-transcellular transport across the blood-brain barrier. Glia. 2016;64(7):1097–123. 10.1002/glia.22960 .26852907 [OpenAIRE] [PubMed] [DOI]

13 Preston JE, Joan Abbott N, Begley DJ. Transcytosis of macromolecules at the blood-brain barrier. Adv Pharmacol. 2014;71:147–63. 10.1016/bs.apha.2014.06.001 .25307216 [OpenAIRE] [PubMed] [DOI]

14 Herve F, Ghinea N, Scherrmann JM. CNS delivery via adsorptive transcytosis. AAPS J. 2008;10(3):455–72. 10.1208/s12248-008-9055-2 .18726697 [OpenAIRE] [PubMed] [DOI]

15 Wioland L, Dupont JL, Bossu JL, Popoff MR, Poulain B. Attack of the nervous system by Clostridium perfringens Epsilon toxin: from disease to mode of action on neural cells. Toxicon. 2013;75:122–35. 10.1016/j.toxicon.2013.04.003 .23632158 [OpenAIRE] [PubMed] [DOI]

120 references, page 1 of 8
Abstract
Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, in...
Subjects
free text keywords: Research Article, Research and Analysis Methods, Bioassays and Physiological Analysis, Cardiovascular Analysis, Blood-Brain Barrier Permeability Assay, Biology and Life Sciences, Anatomy, Nervous System, Central Nervous System, Medicine and Health Sciences, Cell Biology, Cellular Structures and Organelles, Cell Membranes, Coated Pits, Cellular Types, Animal Cells, Epithelial Cells, Endothelial Cells, Biological Tissue, Epithelium, Vesicles, Endosomes, Cell Processes, Cell Death, Imaging Techniques, Fluorescence Imaging, Toxicology, Toxic Agents, Toxins, Pathology and Laboratory Medicine, Immunology, Genetics, Molecular Biology, Microbiology, Parasitology, Virology, Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5, Blood-Brain Barrier, Brain, Animals, Mice, Inbred C57BL, Knockout, Bacterial Toxins, Cell Membrane Permeability, Caveolin 1, Myelin and Lymphocyte-Associated Proteolipid Proteins, Medical Microbiology, EEA1, Chemistry, Dynamin, Transcytosis, Endosome, Caveolae, Blood–brain barrier, medicine.anatomical_structure, medicine, Internalization, media_common.quotation_subject, media_common, Extravasation
Funded by
NIH| Profiling axonal RNA in vivo using a viral TRAP approach.
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 1R21NS105047-01A1
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
,
NIH| MOUSE GENETICS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 2P30CA008748-43
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Molecular phenotyping of cortical cell types in multiple rodent models of ALS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01NS091722-03
  • Funding stream: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Communities
Neuroinformatics
120 references, page 1 of 8

1 Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178–201. 10.1016/j.neuron.2008.01.003 .18215617 [OpenAIRE] [PubMed] [DOI]

2 Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol. 2006;1(3):223–36. 10.1007/s11481-006-9025-3 .18040800 [OpenAIRE] [PubMed] [DOI]

3 Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57(2):173–85. 10.1124/pr.57.2.4 .15914466 [OpenAIRE] [PubMed] [DOI]

4 Engelhardt B. Development of the blood-brain barrier. Cell Tissue Res. 2003;314(1):119–29. 10.1007/s00441-003-0751-z .12955493 [OpenAIRE] [PubMed] [DOI]

5 Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res. 1998;53(6):637–44. 10.1002/(SICI)1097-4547(19980915)53:6<637::AID-JNR1>3.0.CO;2-6 .9753191 [OpenAIRE] [PubMed] [DOI]

6 Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia. 2013;61(12):1939–58. 10.1002/glia.22575 .24123158 [OpenAIRE] [PubMed] [DOI]

7 Abbott NJ, Friedman A. Overview and introduction: the blood-brain barrier in health and disease. Epilepsia. 2012;53 Suppl 6:1–6. 10.1111/j.1528-1167.2012.03696.x .23134489 [OpenAIRE] [PubMed] [DOI]

8 Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7(1):41–53. 10.1038/nrn1824 .16371949 [OpenAIRE] [PubMed] [DOI]

9 Gloor SM, Wachtel M, Bolliger MF, Ishihara H, Landmann R, Frei K. Molecular and cellular permeability control at the blood-brain barrier. Brain Res Brain Res Rev. 2001;36(2–3):258–64. 10.1016/s0165-0173(01)00102-3 .11690623 [OpenAIRE] [PubMed] [DOI]

10 Tietz S, Engelhardt B. Brain barriers: Crosstalk between complex tight junctions and adherens junctions. J Cell Biol. 2015;209(4):493–506. 10.1083/jcb.201412147 .26008742 [OpenAIRE] [PubMed] [DOI]

11 Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol. 2002;38(6):323–37. .12529927 [OpenAIRE] [PubMed]

12 De Bock M, Van Haver V, Vandenbroucke RE, Decrock E, Wang N, Leybaert L. Into rather unexplored terrain-transcellular transport across the blood-brain barrier. Glia. 2016;64(7):1097–123. 10.1002/glia.22960 .26852907 [OpenAIRE] [PubMed] [DOI]

13 Preston JE, Joan Abbott N, Begley DJ. Transcytosis of macromolecules at the blood-brain barrier. Adv Pharmacol. 2014;71:147–63. 10.1016/bs.apha.2014.06.001 .25307216 [OpenAIRE] [PubMed] [DOI]

14 Herve F, Ghinea N, Scherrmann JM. CNS delivery via adsorptive transcytosis. AAPS J. 2008;10(3):455–72. 10.1208/s12248-008-9055-2 .18726697 [OpenAIRE] [PubMed] [DOI]

15 Wioland L, Dupont JL, Bossu JL, Popoff MR, Poulain B. Attack of the nervous system by Clostridium perfringens Epsilon toxin: from disease to mode of action on neural cells. Toxicon. 2013;75:122–35. 10.1016/j.toxicon.2013.04.003 .23632158 [OpenAIRE] [PubMed] [DOI]

120 references, page 1 of 8
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