Functional endothelial progenitor cells selectively recruit neurovascular protective monocyte-derived F4/80+/Ly6c+ macrophages in a mouse model of retinal degeneration

Abstract

Retinitis pigmentosa is a group of inherited eye disorders that result in profound vision loss with characteristic retinal neuronal degeneration and vasculature attenuation. In a mouse model of retinitis pigmentosa, endothelial progenitor cells (EPC) from bone marrow rescued the vasculature and photoreceptors. However, the mechanisms and cell types underlying these protective effects were uncertain. We divided EPC, which contribute to angiogenesis, into two subpopulations based on their aldehyde dehydrogenase (ALDH) activity and observed that EPC with low ALDH activity (Alde-Low) had greater neuroprotection and vasoprotection capabilities after injection into the eyes of an rd1 mouse model of retinitis pigmentosa compared with EPC with high ALDH activity (Alde-High). Of note, Alde-Low EPC selectively recruited F4/80 1 /Ly6c 1 monocyte-derived macrophages from bone marrow into retina through CCL2 secretion. In addition, the mRNA levels of CCR2, the neurotrophic factors TGF-b1 and IGF-1, and the anti-inflammatory mediator interleukin-10 were higher in migrated F4/80 /Ly6c2 resident retinal microglial cells. These results suggest a novel therapeutic approach using EPC to recruit neuroprotective macrophages that delay the progression of neural degenerative disease. STEM CELLS

Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain

“…Interestingly, the Ly6C + (GR1 + )CCR2 + monocytes/macrophage subset that is depleted by the anti-CCR2 antibody is the subset known to preferably infiltrate into tissues and to have increased expression levels of anti-inflammatory cytokines like IL-10 and transforming growth factor beta. 9,13,39 Therefore, we suggest that the more pronounced effect of anti-CCR2 is due to the depletion of the anti-inflammatory effect–producing Ly6C + CCR2 + subset of monocytes/macrophages as opposed to the more general depletion of all monocytes/macrophages when using clodronate liposomes. An alternative possibility would be that the depletion with clodronate liposomes is less efficient or that repopulation is faster after depletion with clodronate liposomes than after depletion with anti-CCR2.…”

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

“…For example, inflammatory cytokines are increasingly recognized as playing an important role in tissue regeneration (45). One group demonstrated that EPC-derived CCL2 recruited neuroprotective microglia in an acute retinal degeneration model (46). Interaction between HA and CD44 has known to induce chemokine expression, which recruits and activates leukocytes (47).…”

CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic inflammation via the PPARγ

“…Results were presented as percent positive cells over total cells per 0.1 mm 2 . Five randomly chosen independent fields were used for quantification according to previously described methods (18,27).…”