Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis.
Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis.
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DOI：
10.1080/09273948.2020.1849735
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发表时间：
2022-05-19
影响因子：
3.3
通讯作者：
Taylor AW
中科院分区：
文献类型：
--
作者：
Ng TF;Manhapra A;Cluckey D;Choe Y;Vajram S;Taylor AW
眼免疫赦免的中枢神经肽介质是α-MSH，可用于治疗抑制实验性自身免疫性葡萄膜炎(EAU)。α-MSH调节免疫活性的一部分是通过其黑素皮质素5受体(MC5r)。α-msh介导的眼免疫赦免机制之一是抑制与抗原提呈细胞处理抗原有关的吞噬酶体活化。因此，我们研究了MC5r的表达在α-MSH治疗EAU后RPE抑制巨噬细胞吞噬酶体激活的恢复中的可能作用。用α-MSH处理的野生型Eau小鼠和Mc5r(−/−)小鼠的原位培养的RPE-眼球的条件培养液处理巨噬细胞吞噬调理的pHrodoRed细菌活组织切片，以检测吞噬溶酶体的激活。此外，还测定了MC5r(−/−)小鼠巨噬细胞的吞噬活性。MC5r(−/−)小鼠经α-MSH治疗后从EAU中恢复的RPE确实抑制野生型巨噬细胞的吞噬小体成熟，但不抑制MC5r(−/−)巨噬细胞的吞噬小体成熟。此外，α-MSH不抑制MC5R(−/−)巨噬细胞的吞噬酶体活化，巨噬细胞的吞噬活性显著增强。随着巨噬细胞活性的增强，EAU MC5R(−/−)视网膜的损伤增加。结果表明，α-MSH治疗EAU可促进视网膜色素上皮的恢复，抑制巨噬细胞内吞噬酶体活化，保护视网膜免受炎性损伤。这依赖于MC5r的表达。此外，通过MC5r，神经肽α-msh潜在地作为巨噬细胞内吞噬小体成熟的动态平衡调节剂。
A central neuropeptide mediator of ocular immune privilege is α-MSH, which can be used to therapeutically suppress experimental autoimmune uveitis (EAU). A part of α-MSH-regulation of immune activity is through its melanocortin 5 receptor (MC5r). One of the mechanisms of ocular immune privilege mediated by α-MSH is RPE suppression of phagolysosome activation associated with antigen presenting cell (APC) processing of antigen. Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of macrophage phagolysosome activation following α-MSH-treatment of EAU. The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(−/−) mice were used to treat macrophages phagocytizing opsonized-pHrodoRed-bacterial bioparticles to assay for phagolysosome activation. In addition, the phagocytic activity of macrophages from MC5r(−/−) mice was assayed. The RPE from MC5r(−/−) mice that have recovered from EAU after α-MSH-therapy do suppress phagosome maturation in wildtype macrophages; but do not suppress phagosome maturation in MC5r(−/−) macrophages. In addition, α-MSH does not suppress phagolysosome activation in MC5r(−/−) macrophages, and the macrophages are highly enhanced in their phagocytic activity. Along with the enhanced macrophage activity was observed an increase in damage of the EAU MC5r(−/−) retinas. The results demonstrated that treatment of EAU with α-MSH mediated recovery of RPE suppression of phagolysosome activation in macrophages and protected the retina from inflammatory damage. This was dependent on the expression of MC5r. Moreover, through MC5r the neuropeptide α-MSH potentially acts as a homeostatic moderator of phagosome-maturation within macrophages.
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DOI：
10.1152/ajpregu.1999.276.5.r1289
发表时间：
1999-05-01
影响因子：
2.8
作者：
Taherzadeh, S;Sharma, S;Lipton, JM
通讯作者：
Lipton, JM
影响因子：
5.6
作者：
Spana, Carl;Taylor, Andrew W.;Dodd, John
通讯作者：
Dodd, John
影响因子：
3.3
作者：
Phan, Toan A.;Taylor, Andrew W.
通讯作者：
Taylor, Andrew W.
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P
影响因子：
5.5
作者：
Lee, Darren J.;Taylor, Andrew W.
通讯作者：
Taylor, Andrew W.