P2 receptor-mediated signaling in mast cell biology

183

153

Neuroinflammation limits tissue damage in response to pathogens or injury and promotes repair. There are two stages of inflammation, initiation and resolution. P2X receptors are gaining attention in relation to immunology and inflammation. The P2X7 receptor in particular appears to be an essential immunomodulatory receptor, although P2X1 and P2X4 receptors also appear to be involved. ATP released from damaged or infected cells causes inflammation by release of inflammatory cytokines via P2X7 receptors and acts as a danger signal by occupying upregulated P2X receptors on immune cells to increase immune responses. The purinergic involvement in inflammation is being explored for the development of novel therapeutic strategies.

Section: Immune Cells and Inflammationmentioning

confidence: 99%

“…P2X receptor expression is also present on microglia, both in vitro and in vivo, particularly P2X4 and P2X7 receptors [93,94]. P2X receptors on mast cells are involved in the pathogenesis of chronic airway allergic inflammation [91].…”

Section: Immune Cells and Inflammationmentioning

confidence: 99%

P2X ion channel receptors and inflammation

Burnstock

2016

183

153

“…ADP and ATP inhibited the generation of TNF-α in response to the TLR2 ligand peptidoglycan, and blocked the production of TNF-γ, IL-8, and MIP-1β in response to leukotriene D4 via P2Y receptors in hMCs for which the presence of P2Y 1 , P2Y 2 , P2Y 11 , P2Y 12 , and P2Y 13 subtypes was confirmed on mRNA level [23]. Finally, ATP has also been reported to be liberated from mast cells itself which could diffuse to elicit responses in distant cells; this ATP release from mast cells is triggered either by FcεR cross-linking, by extracellular nucleotide application, or by mechanic stimulation and is independent on gap-junctional coupling [222,223] .…”

Section: Mast Cellsmentioning

confidence: 99%

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

Jacob

Novo

Bachert

et al. 2013

200

158

Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

“…The class of receptors for extracellular nucleotides comprises eight GPCRs (P2Y 1,2,4,6,11,12,13,14 ) and seven LGICs (P2X 1-7 ), many of which being expressed in blood cells [6]. The roles of P2 receptors in mast cell biology have recently been reviewed [7]. The expression and some functions of human P2X receptors have recently been characterized using both LAD2 mast cells and human lung mast cells [8].…”

Section: Introductionmentioning

confidence: 99%

The role of P2Y14 and other P2Y receptors in degranulation of human LAD2 mast cells

Gao

Wei

Jayasekara

et al. 2012

Mast cell degranulation affects many conditions, e.g., asthma and urticaria. We explored the potential role of the P2Y 14 receptor (P2Y 14 R) and other P2Y subtypes in degranulation of human LAD2 mast cells. All eight P2YRs were expressed at variable levels in LAD2 cells (quantitative real-time RT-PCR). Gene expression levels of ADP receptors, P2Y 1 R, P2Y 12 R, and P2Y 13 R, were similar, and P2Y 11 R and P2Y 4 R were highly expressed at 5.8-and 3.8-fold of P2Y 1 R, respectively. Least expressed P2Y 2 R was 40-fold lower than P2Y 1 R, and P2Y 6 R and P2Y 14 R were ≤50 % of P2Y 1 R. None of the native P2YR agonists alone induced β-hexosaminidase (β-Hex) release, but some nucleotides significantly enhanced β-Hex release induced by C3a or antigen, with a rank efficacy order of ATP>UDPG≥ADP>>UDP, UTP. Although P2Y 11 R and P2Y 4 R are highly expressed, they did not seem to play a major role in degranulation as neither P2Y 4 R agonist UTP nor P2Y 11 R agonists ATPγS and NF546 had a substantial effect. P2Y 1 Rselective agonist MRS2365 enhanced degranulation, but 1,000-fold weaker compared to its P2Y 1 R potency, and the effect of P2Y 6 R agonist 3-phenacyl-UDP was negligible. The enhancement by ADP and ATP appears mediated via multiple receptors. Both UDPG and a synthetic agonist of the P2Y 14 R, MRS2690, enhanced C3a-induced β-Hex release, which was inhibited by a P2Y 14 R antagonist, specific P2Y 14 R siRNA and pertussis toxin, suggesting a role of P2Y 14 R activation in promoting human mast cell degranulation.