Abstract
A central characterization of retinal immunobiology is the prevention of proinflammatory activity by macrophages. The retinal pigment epithelial cells (RPEs) are a major source of soluble anti-inflammatory factors. This includes a soluble factor that induces macrophage apoptosis when the activity of the immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) is neutralized. In this manuscript, isolated extracellular soluble membranes (ESMs) from primary RPE were assayed to see if they could be the soluble mediator of apoptosis. Our results demonstrated that RPE ESMs mediated the induction of macrophage apoptosis that was suppressed by α-MSH. In contrast, the RPE line ARPE-19, cultured under conditions that induce similar anti-inflammatory activity to primary RPEs, did not activate apoptosis in the macrophages. Moreover, only the ESMs from primary RPE cultures, and not those from the ARPE-19 cell cultures, expressed mFasL. The results demonstrate that RPE ESMs are a soluble mediator of apoptosis and that this may be a mechanism by which the RPEs select for the survival of α-MSH-induced suppressor cells.
Highlights
Cells 2021, 10, 1193. https://doi.org/The retinal pigment epithelial cells (RPEs) contribute to the ocular immune privilege by expressing soluble factors [1,2,3,4]
The results demonstrated that the addition of α-MSH suppressed caspase 3 activation in the cultures of RPE-extracellular vesicles (EVs)-treated macrophages
The results demonstrated that extracellular soluble membranes (ESMs) induce apoptosis in macrophages and that α-MSH suppresses the apoptotic signal
Summary
The retinal pigment epithelial cells (RPEs) contribute to the ocular immune privilege by expressing soluble factors [1,2,3,4]. These factors regulate immune cell activity to preserve vision and protect the retina from the deleterious effects of inflammation [5]. The soluble factor is extracellular vesicles (EVs) expressing membrane FasL (mFasL) and TRAIL. These EVs play a part in the required immune regulation to ensure fetal development and live birth
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