Department of Ophthalmology, Boston University School of Medicine, Boston, MA 02118, USA.
Cells. 2021 May 13;10(5):1193. doi: 10.3390/cells10051193.
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.
视网膜免疫生物学的一个主要特征是通过巨噬细胞来预防炎症活动。视网膜色素上皮细胞（RPE）是可溶性抗炎因子的主要来源。其中包括一种可溶性因子，当免疫调节神经肽α-黑色素细胞刺激素（α-MSH）的活性被中和时，该因子会诱导巨噬细胞凋亡。在本手稿中，我们检测了从原代 RPE 中分离的细胞外可溶性膜（ESMs），以确定它们是否可以作为凋亡的可溶性介质。我们的结果表明，RPE ESM 介导了巨噬细胞凋亡的诱导，而α-MSH 抑制了这种诱导。相比之下，在诱导类似于原代 RPE 的抗炎活性的条件下培养的 RPE 细胞系 ARPE-19 并不能激活巨噬细胞中的凋亡。此外，只有原代 RPE 培养物的 ESMs 表达 mFasL，而 ARPE-19 细胞培养物的 ESMs 则没有。这些结果表明，RPE ESM 是凋亡的可溶性介质，这可能是 RPE 选择α-MSH 诱导的抑制细胞存活的机制之一。
