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Microparticles stimulate angiogenesis by inducing ELR(+) CXC-chemokines in synovial fibroblasts.
MedLine Citation:
PMID:  20219013     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Microparticles (MPs) are small membrane-vesicles that accumulate in the synovial fluids of patients with rheumatoid arthritis (RA). In the arthritic joints, MPs induce a pro-inflammatory and invasive phenotype in synovial fibroblasts (SFs). The present study investigated whether activation of SFs by MPs stimulates angiogenesis in the inflamed joints of patients with RA. MPs were isolated from Jurkat cells and U937 cells by differential centrifugation. SFs were co-cultured with increasing numbers of MPs. The effects of supernatants from co-cultures on endothelial cells were studied in vitro and in vivo using MTT assays, annexin V and propidium iodide staining, trans-well migration assays and modified matrigel pouch assays. MPs strongly induced the expression of the pro-angiogenic ELR(+) chemokines CXCL1, CXCL2, CXCL3, CXCL5 and CXCL6 in RASFs. Other vascular growth factors were not induced. Supernatants from co-cultures enhanced the migration of endothelial cells, which could be blocked by neutralizing antibodies against ELR(+) chemokines. Consistent with the specific induction of ELR(+) chemokines, proliferation and viability of endothelial cells were not affected by the supernatants. In the in vivo bio-chamber assay, supernatants from RASFs co-cultured with MPs stimulated angiogenesis with a significant increase of vessels infiltrating into the matrigel chamber. We demonstrated that MPs activate RASFs to release pro-angiogenic ELR(+) chemokines. These pro-angiogenic mediators enhance migration of endothelial cells and stimulate the formation of new vessels. Our data suggest that MPs may contribute to the hypervascularization of inflamed joints in patients with rheumatoid arthritis.
Authors:
Nicole Reich; Christian Beyer; Kolja Gelse; Alfiya Akhmetshina; Clara Dees; Jochen Zwerina; Georg Schett; Oliver Distler; Jörg H W Distler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  15     ISSN:  1582-4934     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-05-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  756-62     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.
Affiliation:
Department for Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany Division of Orthopedic Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany Center of Experimental Rheumatology and Zurich Center of Integrative Human Physiology, University Hospital Zurich, Zurich, Switzerland.
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