Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 69, Issue 18, Pages 3101-3113Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-0981-x
Keywords
Integrins; Migration; Immobilization; PBMCs; Inflammation
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB Transregio 19, C5]
- Berlin-Brandenburg School for Regenerative Therapies, Deutsche Forschungsgemeinschaft Graduate School [203]
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In this study, we performed a comprehensive analysis of the effect of CCN1 on the migration of human immune cells. The molecule CCN1, produced by fibroblasts and endothelial cells, is considered as an important matrix protein promoting tissue repair and immune cell adhesion by binding various integrins. We recently reported that CCN1 therapy is able to suppress acute inflammation in vivo. Here, we show that CCN1 binds to various immune cells including T cells, B cells, NK cells, and monocytes. The addition of CCN1 in vitro enhances both actin polymerization and transwell migration. Prolonged incubation with CCN1, however, results in the inhibition of migration of immune cells by a mechanism that involves downregulation of PI3K gamma, p38, and Akt activation. Furthermore, we observed that immune cells themselves produce constitutively CCN1 and secretion is induced by pro-inflammatory stimuli. In line with this finding, patients suffering from acute inflammation had enhanced serum levels of CCN1. These findings extend the classical concept of CCN1 as a locally produced cell matrix adhesion molecule and suggest that CCN1 plays an important role in regulating immune cell trafficking by attracting and locally immobilizing immune cells.
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