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K.L. Lew, S.W. McPherson, N.D. Heuss, D.S. Gregerson; Galectins Play a Role in the Immunomodulatory Repertoire of Corneal Endothelial Cells and Retinal Pigment Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):740.
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© ARVO (1962-2015); The Authors (2016-present)
Introduction: Galectins 1 and 3 are members of a family of carbohydrate-binding proteins. The proteins share a carbohydrate binding domain with specificity for galactose-containing glycoconjugates. This binding is inhibited to a significant degree by beta-D-lactose. An unusual array of activities has been assigned to the various family members, including galectins-1 and -3. Most studies have examined their effects on cell cycling. We have found galectin-1 and galectin-3 in corneal endothelial (CE) cells and retinal pigment epithelial (RPE) cells, and find that they have immunoregulatory properties. Methods: RT-PCR was used to detect mRNA for galectins-1 and 3. A monoclonal Ab was used to detect intracellular and cell surface galectin-3 by flow cytometry. Cytokine ELISA’s for IL-2, 4, 6, and 10; IFN-γand TNF-α were done to assay for effects on cytokine production by lymphocytes, CE cells, and RPE cells, and co-cultures of these cells. Results: RT-PCR reveals mRNA for galectin-1 and -3 in our CE and RPE cells. By flow cytometry, we can show intracellular galectin-3 in CE and RPE cells, both resting and endotoxin (LPS) activated. Addition of anti-galectin-3 mAb to CE and RPE cells stimulates production of large amounts IL-6. Co-culture of CE and RPE cells with lymph node cells inhibits the Con A-induced production of IL-2, 4 and IFN-γ. This inhibition is reversed by the addition of the anti-galectin-3 mAb. The mAb reversal of inhibition is itself reversed by adding beta-D-lactose to the cultures. Ligation of galectin-3 with a mAb induces proliferation in T cells that is dependent on the presence of a radiosensitive cell. Conclusions: The galectins are novel activities that are not yet well-characterized in any experimental system. It is curious that both the CE cells and RPE cells, which have unexplained immunoregulatory properties as reported by several labs, produce significant amounts of both of these galectins. Current hypotheses for their function are that they maintain a balance of growth-promoting vs. survival/anti-apoptosis signals that maintain a homeostatic state in cells. We also find clear evidence for immunoregulatory properties.
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