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Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity
We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE). The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831460/ https://www.ncbi.nlm.nih.gov/pubmed/20204129 http://dx.doi.org/10.1155/2010/289360 |
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author | Zhou, Jiehao He, Shikun Zhang, Ning Spee, Christine Zhou, Peng Ryan, Stephen J. Kannan, Ram Hinton, David R. |
author_facet | Zhou, Jiehao He, Shikun Zhang, Ning Spee, Christine Zhou, Peng Ryan, Stephen J. Kannan, Ram Hinton, David R. |
author_sort | Zhou, Jiehao |
collection | PubMed |
description | We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE). The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [(3)H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP-) 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P < .05). Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P < .05) and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier. |
format | Text |
id | pubmed-2831460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-28314602010-03-04 Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity Zhou, Jiehao He, Shikun Zhang, Ning Spee, Christine Zhou, Peng Ryan, Stephen J. Kannan, Ram Hinton, David R. J Biomed Biotechnol Research Article We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE). The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [(3)H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP-) 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P < .05). Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P < .05) and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier. Hindawi Publishing Corporation 2010 2010-03-03 /pmc/articles/PMC2831460/ /pubmed/20204129 http://dx.doi.org/10.1155/2010/289360 Text en Copyright © 2010 Jiehao Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhou, Jiehao He, Shikun Zhang, Ning Spee, Christine Zhou, Peng Ryan, Stephen J. Kannan, Ram Hinton, David R. Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title | Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title_full | Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title_fullStr | Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title_full_unstemmed | Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title_short | Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity |
title_sort | neutrophils compromise retinal pigment epithelial barrier integrity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831460/ https://www.ncbi.nlm.nih.gov/pubmed/20204129 http://dx.doi.org/10.1155/2010/289360 |
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