Extracellular adenine nucleotides inhibit the release of major monocyte recruiters by human monocyte‐derived dendritic cells

Abstract

Extracellular ATP is known to affect the maturation of monocyte-derived dendritic cells mainly by regulation of cytokines and costimulatory molecules. The present study describes the inhibition of MCP-1 (CCL2) and MIP-1a (CCL3) release by human monocyte-derived dendritic cells in response to adenine nucleotides. Our pharmacological data support the involvement of P2Y 11 and P2Y 1 purinergic receptors in the downregulation of these major monocyte recruiters. Migration assays have demonstrated that supernatants of dendritic cells treated with adenine nucleotides or anti-MCP-1/MIP-1a blocking antibodies display a strongly reduced capacity to attract monocytes and immature dendritic cells.

Modulation of murine dendritic cell function by adenine nucleotides and adenosine: Involvement of the A2B receptor

“…We have shown that NECA has an impressive effect on gene expression in LPSstimulated murine BMDC. Some regulations are similar to what has been observed in ATPcS-treated human DC: up-regulation of TSP-1 [11] and VEGF [43], down-regulation of CCL2 and CCL3 [44]. On the contrary, some regulations were not observed in murine BMDC, e.g.…”

Gene Expression Profiling Defines ATP as a Key Regulator of Human Dendritic Cell Functions

“…PGE 2 effects on DC maturation are likely to result from activation of the EP2/EP4 receptors (14). Many of the effects of ATP␥S on MoDCs, such as its effect on CD83 expression and TSP-1 release, are reproduced by forskolin or dibutyryl-cAMP, demonstrating their action through cAMP elevation (4,5,11,14).…”

“…We first performed a selection of sequences regulated at least 2-fold for at least for one agent and one time point (see Table S1 in the supplementary data). 5 Among these 3,512 regulated sequences, 1,896 oligonucleotides were regulated at least 2-fold by ATP␥S and only 97 oligonucleotides were regulated at least 2-fold by PGE 2 . From these experiments, it thus appeared that ATP␥S was able to induce a very wide and early gene expression profile in MoDCs.…”

“…In human monocyte-derived DCs (MoDCs), ATP, which is released inter alia from necrotic cells, induces the upregulation of costimulatory molecules (2-4) and regulates various chemokines and chemokine receptors (5,6). ATP also regulates the action of LPS and other maturating agents on human DCs by inhibiting the production of proinflammatory cytokines such as IL-12, IL-1␤, TNF-␣, and IL-6 and by potentiating anti-inflammatory IL-10 (2, 7).…”

Purinergic Signaling in the Airways

“…Evidence has been presented that P2Y 1 receptors are involved in allergic airway inflammation, which could be at least partly explained by its role in the regulation of dendritic cell maturation (Maitre et al, 2008). Extracellular adenine nucleotides inhibit the release of major monocyte recruiters by human monocytederived dendritic cells and pharmacological data support the involvement of P2Y 11 and P2Y 1 purinergic receptors (Horckmans et al, 2006). In a recent article, it is proposed that purinergic signaling via P2Y 2 receptors in the respiratory epithelium is a critical sensor for airway exposure to airborne allergens, which may provide novel opportunities to dampen hypersensitivity in the Th2-type immune responses in asthma (Kouzaki et al, 2011).…”