Karl, Mike O. and Kroeger, Wolfram and Wimmers, Soenke and Milenkovic, Vladimir M. and Valtink, Monika and Engelmann, Katrin and Strauss, Olaf (2008) Endogenous Gas6 and Ca2+-channel activation modulate phagocytosis by retinal pigment epithelium. CELLULAR SIGNALLING, 20 (6). pp. 1159-1168. ISSN 0898-6568, 1873-3913
Full text not available from this repository. (Request a copy)Abstract
Mutation or loss of MerTK as well as deficiency of alpha v beta 5-integrins, gives rise to retinal-degeneration due to inefficient phagocytosis of photoreceptor outer-segment fragments by the retinal pigment epithelium (RPE). This study shows that Gas6 expressed endogenously by human RPE promotes phagocytosis. The RPE expresses Gas6 more highly in vivo and in serum-reduced conditions in vitro than in high-serum conditions, suggesting a negative-feedback control. An antibody-blockage approach revealed that Gas6-expressing RPE phagocytizes photoreceptor outer-segment fragments due to stimulation of MerTK by endogenous Gas6 in vitro. MerTK- and Gas6-antibodies reduced phagocytosis. Blocking L-type Ca2+-channels with nifedipine inhibited MerTK dependent phagocytosis in vitro. Application of integrin inhibitory, soluble, RGD-containing peptides or soluble vitronectin reduced L-type Ca2+-channel currents in R-PE. Herbimycin A, which reduces phosphorylation of integrin receptor-associated proteins and decreases L-type Ca2+-channel currents in RPE, eliminates the inhibiting vitronectin effect and abolishes phagocytosis. Thus, Gas6-promoted phagocytosis was inhibited by L-type Ca2+-channel blockage, which in turn may be activated by integrin receptor stimulation. These results, suggest that L-type Ca2+-channels could be regulated downstream of both MerTK and alpha v beta 5-integrin, indicating that the binding and uptake mechanisms of phagocytosis are part of a converging pathway. (C) 2008 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHOTORECEPTOR OUTER SEGMENTS; MER TYROSINE KINASE; ALPHA-V-BETA-5 INTEGRIN; APOPTOTIC CELLS; GROWTH ARREST; PROTEIN-S; RCS-RAT; MACULAR DEGENERATION; RECEPTOR ACTIVATION; SPLICE VARIANT; Ca2+-channels; Gas6; integrin; MerTK; phagocytosis; retinal pigment epithelium |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Oct 2020 11:57 |
| Last Modified: | 29 Oct 2020 11:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30774 |
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