13 research outputs found
The role of 90Y-radioembolization in downstaging primary and secondary hepatic malignancies: a systematic review
Stereology: a simplified and more time-efficient method than planimetry for the quantitative analysis of vascular structures in different models of intimal thickening
Oxidized low-density lipoprotein stimulates dendritic cells maturation via LOX-1-mediated MAPK/NF-κB pathway
Transient decrease in human peripheral blood myeloid dendritic cells following influenza vaccination correlates with induction of serum antibody
Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells
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 surface-expressed phosphatidylserine (PS) with a variant of annexin A5 (Arg-Gly-Asp-annexin A5, RGD-anxA5) that has gained the function to interact with alpha(v)beta(3) receptors of the phagocyte. We describe design and characterization of RGD-anxA5 and show that introduction of RGD transforms anxA5 from an inhibitor into a stimulator of efferocytosis. RGD-anxA5 enhances engulfment of apoptotic cells by phorbol-12-myristate-13-acetate-stimulated THP-1 (human acute monocytic leukemia cell line) cells in vitro and resident peritoneal mouse macrophages in vivo. In addition, RGD-anxA5 augments secretion of interleukin-10 during efferocytosis in vivo, thereby possibly adding to an anti-inflammatory environment. We conclude that targeting cell surface-expressed PS is an attractive strategy for treatment of inflammatory diseases and that the rationally designed RGD-anxA5 is a promising therapeutic agent