Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity. (3rd March 2010)

• Record Type: Journal Article
• Authors: Zhou, Jiehao; He, Shikun; Zhang, Ning; Spee, Christine; Zhou, Peng; Ryan, Stephen J.; Kannan, Ram; Hinton, David R.
• Other Names: Chai Karl Academic Editor.
• Is Part Of: Journal of biomedicine and biotechnology. Volume 2010(2010)
• Publication Date: 2010-03-03
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Medicine; Biology; Biotechnology; Médecine; Biologie; Biotechnologie; Biology; Biotechnology; Medicine; Biotechnology; Biomedicine; Electronic journals; Periodical; Periodicals; Electronic journals; 610
• DOI: 10.1155/2010/289360
• Languages: English
• ISSNs: 1110-7243

Abstract

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.