RT Journal Article
T1 Synoviocyte-Derived CXCL12 Is Displayed on Endothelium and Induces Angiogenesis in Rheumatoid Arthritis
A1 Pablos Álvarez, José Luis
A1 Santiago, Begoña
A1 Galindo Izquierdo, María
A1 Torres, Carmen
A1 Brehmer, María T.
A1 Blanco, Francisco J.
A1 García Lázaro, Francisco J.
AB CXCL12 (stromal cell-derived factor-1) is a potent CXC chemokine that is constitutively expressed by stromal resident cells. Although it is considered a homeostatic rather than an inflammatory chemokine, CXCL12 has been immunodetected in different inflammatory diseases, but also in normal tissues, ant its potential functions and regulation in inflammation are not well known. In this study, we examined the cellular sources of CXCL12 gene expression and the mechanism and effects of its interactions with endothelial cells in rheumatoid arthritis synovium. We show that CXCL12 mRNA was not overexpressed nor induced in cultured rheumatoid synoviocytes, but it specifically accumulated in the rheumatoid hyperplastic lining layer and endothelium. CXCL12 gene expression was restricted to fibroblast-like synoviocytes, whereas endothelial cells did not express CXCL12 mRNA, but displayed the protein on heparitinase-sensitive factors. CXCL12 colocalized with the angiogenesis marker alpha(v)beta(3) integrin in rheumatoid endothelium and induced angiogenesis in s.c. Matrigel plugs in mice. The angiogenic activity of rheumatoid synovial fluid in vivo was abrogated by specific immunodepletion of CXCL12. Our results indicate that synoviocyte-derived CXCL12 accumulates and it is immobilized on heparan sulfate molecules of endothelial cells, where it can promote angiogenesis and inflammatory cell infiltration, supporting a multifaceted function for this chemokine in the pathogenesis of rheumatoid arthritis.
PB American Association of Immunologists
SN 0022-1767
YR 2003
FD 2003-02-15
LK https://hdl.handle.net/20.500.14352/114233
UL https://hdl.handle.net/20.500.14352/114233
LA eng
NO Pablos JL, Santiago B, Galindo M, Torres C, Brehmer MT, Blanco FJ, García-Lázaro FJ. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol. 2003 Feb 15;170(4):2147-52.
NO Ministerio de Ciencia y Tecnología (España)
DS Docta Complutense
RD 9 abr 2025