2012
DOI: 10.1038/cdd.2012.107
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Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells

Abstract: Impaired efferocytosis has been shown to be associated with, and even to contribute to progression of, chronic inflammatory diseases such as atherosclerosis. Enhancing efferocytosis has been proposed as strategy to treat diseases involving inflammation. Here we present the strategy to increase 'eat me' signals on the surface of apoptotic cells by targeting cell surfaceexpressed phosphatidylserine (PS) with a variant of annexin A5 (Arg-Gly-Asp-annexin A5, RGD-anxA5) that has gained the function to interact with… Show more

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Cited by 32 publications
(32 citation statements)
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“…Only recently, an AnxA5 variant was used as therapeutic agent to increase the phagocytosis of dying cells in vivo [Schutters et al, 2013] and a homodimer of AnxA5 was developed to prolong blood circulation time and inhibit thrombus formation in vivo [Rand et al, 2012]. Our results now confirm that AnxA5 can be used to delay coagulation in vivo at similar concentrations compared to the previous study (1 vs. 2 μg/g body weight of the mouse).…”
Section: Discussionsupporting
confidence: 79%
“…Only recently, an AnxA5 variant was used as therapeutic agent to increase the phagocytosis of dying cells in vivo [Schutters et al, 2013] and a homodimer of AnxA5 was developed to prolong blood circulation time and inhibit thrombus formation in vivo [Rand et al, 2012]. Our results now confirm that AnxA5 can be used to delay coagulation in vivo at similar concentrations compared to the previous study (1 vs. 2 μg/g body weight of the mouse).…”
Section: Discussionsupporting
confidence: 79%
“…Our observations on plaque composition are in line with a previous study, in which exogenous anxA5 did not change plaque collagen content, acellular mass and smooth muscle cell content in advanced atherosclerosis, 9 suggesting that the anti-inflammatory effects of anxA5 may be balanced by its inhibitory effects on efferocytosis. 28,29 PS on the surface of apoptotic cells skewed macrophages towards an antiinflammatory phenotype. 30 AnxA5 may inhibit this pathway by shielding PS on the surface of apoptotic cells.…”
Section: Discussionmentioning
confidence: 99%
“…An alternative strategy to repair the engulfment synapse is based on the improved opsonization of phosphatidylserine on apoptotic cells. 124 Herein, a fusion protein of Annexin V (which binds to phosphatidylserine) and a Arg-Gly-Asp motif (which binds to vitronectin receptor on efferocytes) enhances phagocytic clearance. 124 Finally, a nanoparticle-based delivery approach using a fragment of the resolving protein Annexin A1 reduced inflammation and provided functional improvement in a mouse model of hindlimb ischemia.…”
Section: Circulation Researchmentioning
confidence: 99%