STUDY OF LRP1 LIGANDS AS MODULATORS OF MICROGLIA-MACROPHAGE CROSSTALK UNDER INFLAMMATORY CONDITIONS

Age-related Macular Degeneration (AMD) is a retinal disease responsible for blindness in adults over 65 years. In its neovascular stage (nAMD), mononuclear phagocytes (MPs) accumulate and induce an inflammatory environment that drives pathological choroidal neovascularization (CNV). LRP1, a receptor expressed in MPs, acts as an anti-inflammatory receptor in various pathologies when activated by ligands like activated alpha-2-Macroglobulin (α2M*) and SP16. Our aim was to evaluate the effect of LRP1 ligands on MPs under inflammatory conditions. BV2 microglia and bone marrow-derived macrophages (BMDMs) were pretreated with LRP1 ligands for 30 min before LPS stimulation. Western blot analysis revealed reduced TNFα expression, wound healing assays showed reduced migration areas, and flow cytometry in BMDMs, attenuated the reduction in the LRP1high subpopulation produced under LPS stimulation (microglia do not present two LRP1 subpopulations). Additionally, BV2 supernatant collected after 2h of LRP1 ligand treatment was used as conditioned medium on BMDMs for 30 min before LPS stimulation. We observed reduced TNFα levels, and a decrease in CD86+ BMDMs, with LRP1high subpopulation restore. In conclusion, these results suggest that LRP1 ligands on microglia and macrophages have an anti-inflammatory effect. Also, LRP1 ligands on microglia promotes the release of soluble mediators that exert similar effects on macrophages. Further studies are needed to understand involved mechanisms.