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Atsuko Fujii, Ayumi Morimoto-Tochigi, Ryan D. Walkup, Thomas R. Shearer, Mitsuyoshi Azuma; Lacritin-Induced Secretion of Tear Proteins From Cultured Monkey Lacrimal Acinar Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(4):2533-2540. doi: https://doi.org/10.1167/iovs.12-10394.
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© ARVO (1962-2015); The Authors (2016-present)
During inflammation of the ocular surface, increased proinflammatory cytokines depress tear protein secretion, suggesting that a decline in lacrimal cell function contributes to dry eye. Lacritin, a glycoprotein secreted from lacrimal acinar cells, may function as an autocrine factor to stimulate tear protein secretion. The purpose of the present experiment was to investigate lacritin-induced protein secretion in normal and cytokine-pretreated (inflammation model) monkey acinar cells.
Acinar cells from monkey lacrimal glands were cultured with or without tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ). Protein secretion was induced by lacritin or carbachol (Cch, positive control). Proteins were detected and identified by immunoblotting and immunocytochemistry. Intracellular Ca2+ was measured with the fluorophore Calcium-4, and cell damage was determined by LDH leakage into the culture medium.
In cultured monkey acinar cells, lacritin stimulated tear protein secretion in normal cells without elevating intracellular Ca2+. In contrast, Cch elevated intracellular Ca2+ and release of tear proteins. This contrast suggested an alternate, calcium-independent mechanism for lacritin-induced protein secretion. TNF-α plus IFN-γ caused LDH leakage from sensitive human corneal epithelial cells, but even higher doses of TNF-α plus IFN-γ did not cause LDH leakage from monkey acinar cells, suggesting a higher tolerance against these cytokines. In cytokine-treated acinar cells, lacritin stimulated protein secretion as much as that in normal cells. In contrast, Cch-induced elevation of Ca2+ and release of proteins were depressed by cytokines.
Lacritin might be a useful biotechnology-based treatment agent against ocular surface diseases where endogenous lacritin is inadequate.
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