Ocular immunomodulating neuropeptides alpha-MSH and neuropeptide Y modulate phagocytic activity of the microphage cell line RAW 246.7
Phan, Toan Anh
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The eye is an immune privileged tissue. Within the ocular microenvironment, there are regulatory mechanisms that suppress inflammation. These anti-inflammatory mechanisms are partly mediated by immunomodulating neuropeptides. We previously found that alpha-melanocyte stimulating hormone (α-MSH) and Neuropeptide Y (NPY) together induce activation of myeloid suppressor-like macrophages. In this study, we examined the possibility that α-MSH and NPY also modulate phagocytosis by macrophages. The monocytic cell line RAW 246.7 was treated with α-MSH and NPY at 1 ng/ml each, a concentration produced by retinal pigment epithelial cells in culture. The treated cells were fed florescent bioparticles of Gram(-) E. Coli or Gram(+) S. Aureus with or without opsin and assayed by flow cytometry. Also tested were the formation of phagolysosomes using pH sensitive florescent E. Coli or S. Aureus bioparticles with or without opsin, and the level of mannose receptors. The a MSH and NPY treated macrophages were significantly suppressed in their capacity to phagocytize unopsonized E. coli; however, suppression of S. Aureus phagocytosis was limited to NPY treated macrophages. In addition, α-MSH and NPY co-treatment suppressed phagocytosis and phagolysosome formation in the macrophages. Fluorescent microscopy imaging showed that there was a qualitative change in phagolysosome formation in opsonized bioparticle conjugates corresponding to the change seen in relative intensity measurements. There was no significant change in the number of man nose receptors in α-MSH, NPY, or α-MSH and NPY treated cells. As α-MSH and NPY together can induce suppressor macrophages within the ocular microenvironment, they can also modulate in a stimulus-dependent manner phagocytic signals within the macrophages. Therefore while the eye is protecting itself from the damaging effects of inflammation it may be making itself vulnerable by having less than optimal innate immune clearance of infectious pathogens.
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