Junctional adhesion molecule-C is a soluble mediator of angiogenesis

• Published in: The Journal of immunology (1950) Vol. 185; no. 3; pp. 1777 - 1785
• Main Authors: Rabquer, Bradley J, Amin, Mohammad A, Teegala, Nanditha, Shaheen, Matthew K, Tsou, Pei-Suen, Ruth, Jeffrey H, Lesch, Charles A, Imhof, Beat A, Koch, Alisa E
• Format: Journal Article
• Language: English
• Published: United States 01.08.2010
• Subjects: Animals; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - pathology; Arthritis, Rheumatoid - therapy; Cell Adhesion Molecules - blood; Cell Adhesion Molecules - physiology; Cell Adhesion Molecules - therapeutic use; Cell Line, Transformed; Cell Movement - immunology; Cells, Cultured; Humans; Immunoglobulins - blood; Immunoglobulins - physiology; Immunoglobulins - therapeutic use; Inflammation Mediators - blood; Inflammation Mediators - physiology; Inflammation Mediators - therapeutic use; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - immunology; Receptors, Cell Surface; Solubility; Synovial Fluid - immunology; Synovial Fluid - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000556

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed by endothelial cells (ECs) that plays a role in tight junction formation, leukocyte adhesion, and transendothelial migration. In the current study, we investigated whether JAM-C is found in soluble form and whether soluble JAM-C (sJAM-C) mediates angiogenesis. We found that JAM-C is present in soluble form in normal serum and elevated in rheumatoid arthritis (RA) serum. The concentration of sJAM-C is also elevated locally in RA synovial fluid compared with RA serum or osteoarthritis synovial fluid. sJAM-C was also present in the culture supernatant of human microvascular ECs (HMVECs) and immortalized human dermal microvascular ECs, and its concentration was increased following cytokine stimulation. In addition, sJAM-C cleavage from the cell surface was mediated in part by a disintegrin and metalloproteinases 10 and 17. In functional assays, sJAM-C was both chemotactic and chemokinetic for HMVECs and induced HMVEC tube formation on Matrigel in vitro. Neutralizing anti-JAM-C Abs inhibited RA synovial fluid-induced HMVEC chemotaxis and sJAM-C-induced HMVEC tube formation on Matrigel. sJAM-C also induced angiogenesis in vivo in the Matrigel plug and sponge granuloma models. Moreover, sJAM-C-mediated HMVEC chemotaxis was dependent on Src, p38, and PI3K. Our results show that JAM-C exists in soluble form and suggest that modulation of sJAM-C may provide a novel route for controlling pathological angiogenesis.