Induction of apoptosis in circulating angiogenic cells by microparticles.

Distler J, Akhmetshina A, Dees C, Juengel A, Stürzl M, Gay S, Pisetsky DS, Schett G, Distler O (2011)

Publication Status: Published

Publication Type: Journal article

Publication year: 2011

Journal

Book Volume: 63

Pages Range: 2067-77

Journal Issue: 7

DOI: 10.1002/art.30361

Abstract

Systemic sclerosis (SSc) is an autoimmune disease marked by aberrant activation and apoptosis of endothelial cells (ECs) and decreased numbers of circulating angiogenic cells (CACs). The aim of this study was to analyze whether microparticles might link pathologic activation and apoptosis of ECs with reduced numbers of CACs.\nApoptosis was quantified by staining for annexin V and measurement of caspase 3 activity. The uptake of microparticles by CACs was determined by fluorescence-activated cell sorting and by fluorescence microscopy. Tritiated arachidonic acid and phosphatidylinositol 3,5-bisphosphate were used to demonstrate the transfer of arachidonic acid and highlight the role of the acid sphingomyelinase in microparticle-induced apoptosis of endothelial progenitor cells.\nMicroparticles derived from activated or apoptotic ECs, the expression of which is strongly increased in the blood of patients with SSc, induce apoptosis in CACs in a dose-dependent manner. Microparticles, which are rich in arachidonic acid, are phagocytosed by CACs. Inhibition of phagocytosis prevents the induction of apoptosis in CACs by microparticles. Microparticles can transport arachidonic acid from ECs to CACs, and purified arachidonic acid mimics the proapoptotic effects of microparticles. Arachidonic acid activates the acid sphingomyelinase, and inhibition of acid sphingomyelinase prevents microparticle-induced apoptosis of CACs. Thus, phagocytosis of microparticles might stimulate the activity of acid sphingomyelinase and activate the apoptotic machinery.\nThe induction of apoptosis in CACs by microparticles derived from ECs provides a novel link between aberrant activation or apoptosis of ECs, decreased numbers of CACs, and impaired formation of new vessels in SSc.\nOBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION

Authors with CRIS profile

Involved external institutions

Universitätsspital Zürich (USZ) Switzerland (CH) Durham VA Medical Center United States (USA) (US)

How to cite

APA:

Distler, J., Akhmetshina, A., Dees, C., Juengel, A., Stürzl, M., Gay, S.,... Distler, O. (2011). Induction of apoptosis in circulating angiogenic cells by microparticles. Arthritis & Rheumatism-Arthritis Care & Research, 63(7), 2067-77. https://doi.org/10.1002/art.30361

MLA:

Distler, Jörg, et al. "Induction of apoptosis in circulating angiogenic cells by microparticles." Arthritis & Rheumatism-Arthritis Care & Research 63.7 (2011): 2067-77.

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