The Neuropeptides of Ocular Immune Privilege, ?-MSH and NPY, Suppress Phagosome Maturation in Macrophages.

ABSTRACT: The ocular microenvironment has evolutionarily adapted several mechanisms of immunosuppression to minimize the induction of inflammation. Neuropeptides produced by the retinal pigment epithelial cells regulate macrophage activity. Two neuropeptides, ?-melanocyte-stimulating hormone (? -MSH) and neuropeptide Y (NPY), are constitutively expressed by the retinal pigment epithelial cells. Together these two neuropeptides induce anti-inflammatory cytokine production in endotoxin-stimulated macrophages and suppress phagocytosis of unopsonized bioparticles. These neuropeptides do not suppress the phagocytosis of opsonized bioparticles; however, they do suppress phagolysosome activation or formation. In this report, we studied the possibility that ?-MSH with NPY suppress phagosome maturation within macrophages using opsonized OVA-coated magnetic beads to isolate and analyze the phagosomes. The magnetic bead-containing intercellular vesicles were isolated and assayed for Rab5, Rab7, LAMP1, Iad, and OVA. The macrophages cotreated with ?-MSH and NPY were suppressed in Rab7 recruitment to the phagosome with suppression in LAMP1 expression but not in Iad expression. The results demonstrated that the ?-MSH/NPY cotreatment suppressed phagosome maturation. In addition, the a-MSH/NPY-cotreated macrophages were suppressed in their ability to Ag stimulate CD4+ T cell proliferation. These results imply a potential mechanism of ocular immune privilege to divert Ag processing to prevent autoreactive effector T cells from binding their target cognate Ag within the ocular microenvironment.

SUBMITTER: Benque IJ 

PROVIDER: S-EPMC6319950 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature