Recent studies have identified two subsets of blood monocytes based on their expression of CX
3CR1. High expression identified a population associated with immune surveillance and precursors of resident tissue macrophages. CX
3R1
lo have been found to infiltrate sites of inflammation, possibly via CCR2, and may be precursors of circulating dendritic cells. Moreover, binding of CX
3L1 was suggested to provide a survival signal to CX
3R1
hi monocytes.
22 In support of this CX
3CR1
+ microglia express CD95 and CD95L, and CX
3CL1 treatment of microglia maintains cell survival and inhibits Fas-ligand induced apoptosis in vitro. Survival is related to inhibition of the proapoptotic molecules BAD and BID and upregulation of Bcl-x
L. 23 Therefore, it is possible that CX
3CR1 M280, which is related to reduced function, affects recruitment of CX
3R1
hi resident monocyte precursors, but has little influence on inflammatory monocytes. Of note, in support of this hypothesis, monocytes have a sentinel protective role against age-related macular degeneration.
24 An association between CX
3CR1 I249 and M280 has been described in patients with AMD compared with control subjects. Moreover, retinal cells microdissected from AMD and normal archival tissue were analyzed in a recent study. The M280 allele was found at a significantly higher frequency in cells from patients with AMD than in the normal population. Moreover, cells from patients with AMD had less CX
3CR1 transcript and protein, which suggests that both altered function and expression of CX
3CR1 contribute to AMD, possibly through a decrease in chemoattraction of inflammatory cells.
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