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Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity
- Source :
- Journal of Biomedicine and Biotechnology, Vol 2010 (2010), Journal of Biomedicine and Biotechnology
- Publication Year :
- 2010
- Publisher :
- Hindawi Limited, 2010.
-
Abstract
- 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[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.
- Subjects :
- Male
Article Subject
Neutrophils
lcsh:Biotechnology
Health, Toxicology and Mutagenesis
lcsh:Medicine
Retinal Pigment Epithelium
Matrix Metalloproteinase Inhibitors
Biology
Matrix metalloproteinase
Occludin
Tight Junctions
Mice
chemistry.chemical_compound
Western blot
lcsh:TP248.13-248.65
Genetics
medicine
Animals
Molecular Biology
Incubation
Cells, Cultured
Retinal pigment epithelium
Ussing chamber
medicine.diagnostic_test
Tight junction
Choroid
Histocytochemistry
lcsh:R
Membrane Proteins
Retinal
General Medicine
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Matrix Metalloproteinase 9
chemistry
Molecular Medicine
Cattle
sense organs
Research Article
Biotechnology
Subjects
Details
- ISSN :
- 11107251 and 11107243
- Volume :
- 2010
- Database :
- OpenAIRE
- Journal :
- Journal of Biomedicine and Biotechnology
- Accession number :
- edsair.doi.dedup.....1dfbc4b74a21041120dbbb85329cff5a