Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells
| Autor: | Dennis H. M. Kusters, Martijn L. Chatrou, Trinidad Montero-Melendez, Chris P. M. Reutelingsperger, Mauro Perretti, Peter Vandenabeele, Kristof Schutters, Marjo M. P. C. Donners, Dmitri V. Krysko, Leon J. Schurgers, Niko Deckers |
|---|---|
| Přispěvatelé: | Promovendi CD, Biochemie, Moleculaire Genetica, Ondersteunend personeel CD, RS: CARIM School for Cardiovascular Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
phosphatidylserine
Phagocyte Phagocytosis Inflammation Phosphatidylserines Biology Jurkat cells Monocytes Cell Line Jurkat Cells Mice medicine Cell Adhesion Animals Humans THP1 cell line Molecular Targeted Therapy Efferocytosis Molecular Biology efferocytosis Original Paper Microscopy Confocal Macrophages Cell Membrane apoptosis annexin A5 Cell Biology Cell biology Mice Inbred C57BL medicine.anatomical_structure Apoptosis medicine.symptom Annexin A5 Oligopeptides |
| Zdroj: | Cell Death and Differentiation, 20(1), 49-56. Nature Publishing Group |
| ISSN: | 1350-9047 |
| Popis: | 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. Cell Death and Differentiation (2013) 20, 49-56; doi:10.1038/cdd.2012.107; published online 7 September 2012 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|