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Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node–directing chemokine CCL19
- Source :
- Blood; February 2006, Vol. 107 Issue: 4 p1537-1545, 9p
- Publication Year :
- 2006
-
Abstract
- Dendritic-cell (DC) migration to secondary lymphoid organs is crucial for the initiation of adaptive immune responses. Although LPS up-regulates CCR7 on DCs, a second signal is required to enable them to migrate toward the chemokine CCL19 (MIP-3β). We found that the nitric oxide (NO) donor NOR4 provides a signal allowing LPS-stimulated DCs to migrate toward CCL19. NO affects DC migration through both the initial activation of the cGMP/cGMP kinase (cGMP/cGK) pathway and a long-term effect that reduced cGK activity via negative feedback. Indeed, migration of DCs toward CCL19, unlike migration toward CXCL12 (SDF-1α), required inhibition of cGK. LPS increased both cGK expression and cGK activity as measured by phosphorylation of the key cGK target vasodilator-stimulated phosphoprotein (VASP). Because cGK phosphorylation of VASP can disrupt focal adhesions and inhibit cell migration, LPS-induced VASP phosphorylation may prevent DCs from migrating without a second signal. Long-term NOR4 treatment inhibited the increase in cGK-dependent VASP phosphorylation, releasing this brake so that DCs can migrate. NO has been implicated in the regulation of autoimmunity through its effect on T cells. Our results suggest that NO regulation of DC migration and cytokine production may contribute to the protective effects of NO in autoimmune disorders.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 107
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs57041078
- Full Text :
- https://doi.org/10.1182/blood-2005-07-2901