IL-18 associates to microvesicles shed from human macrophages by a LPS/TLR-4 independent mechanism in response to P2X receptor stimulation.

Extracellular ATP, released upon microbial infection, cell damage, or inflammation, acts as an alert signal toward immune cells by activating P2 receptors. The nucleotide causes microvesicle (MV) shedding from immune and nonimmune cells. Here, we show that IL-18 associates with MVs shed by human ex vivo macrophages upon P2X receptor stimulation.

Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation.

It has been reported that ATP inhibits or stimulates lymphoid cell proliferation depending on the cellular subset analyzed. In this study, we show that ATP exerts strikingly opposite effects on anti-CD3/CD28-activated and regulatory CD4(+) T cells (T(regs)), based on nucleotide concentration. We demonstrate that physiological concentrations of extracellular ATP (1-50 nM) do not affect activated CD4(+) T cells and T(regs).

Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice.

Extracellular ATP and UTP nucleotides increase the proliferation and engraftment potential of normal human hematopoietic stem cells via the engagement of purinergic receptors (P2Rs). In the present study, we show that ATP and UTP have strikingly opposite effects on human acute myeloblastic leukemia (AML) cells. Leukemic cells express P2Rs.

Purinergic stimulation of human mesenchymal stem cells potentiates their chemotactic response to CXCL12 and increases the homing capacity and production of proinflammatory cytokines.

Objective: Extracellular adenosine triphosphate (ATP) is a well-recognized mediator of cell-to-cell communication. Here we show ATP effects on bone marrow (BM)-derived human mesenchymal stem cell (hMSCs) functions.

Materials And Methods: ATP-induced modification of hMSCs gene expression profile was assessed by Affymetrix technology.

ATP secreted by endothelial cells blocks CX₃CL 1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y₁₁ receptor activation.

Endothelial cells (ECs) represent a major source of actively secreted adenosine triphosphate (ATP). Natural killer (NK) cells can mediate vascular injury in several pathologic conditions, including cytomegalovirus infection and vascular leak syndrome. We studied NK-cell expression of P2 receptors and the role of these nucleotide receptors in the regulation of endothelial-NK cell cross-talk.

Extracellular ATP acting at the P2X7 receptor inhibits secretion of soluble HLA-G from human monocytes.

Bacterial LPS induces the release of ATP from immune cells. Accruing evidence suggests that extracellular ATP participates in the inflammatory response as a proinflammatory mediator by activating the inflammasome complex, inducing secretion of cytokines (IL-1, IL-18) and cell damaging agents such as oxygen radicals, cationic proteins, and metalloproteases. It is not known whether ATP can also act as a proinflammatory mediator by inhibiting production of molecules down-modulating the immune response.

The human cathelicidin LL-37 modulates the activities of the P2X7 receptor in a structure-dependent manner.

Extracellular ATP, released at sites of inflammation or tissue damage, activates the P2X(7) receptor, which in turn triggers a range of responses also including cell proliferation. In this study the ability of the human cathelicidin LL-37 to stimulate fibroblast growth was inhibited by commonly used P2X(7) blockers. We investigated the structural requirements of the growth-promoting activity of LL-37 and found that it did not depend on helix sense (the all-d analog was active) but did require a strong helix-forming propensity in aqueous solution (a scrambled analog and primate LL-37 orthologs devoid of this property were inactive).

Increased P2X7 receptor expression and function in thyroid papillary cancer: a new potential marker of the disease?

Nucleotides are increasingly recognized as nonredundant extracellular signals for chemotaxis, cell growth, and cytokine release. Effects of extracellular nucleotides are mediated by P2 receptors, among which the P2X(7) subtype is attracting increasing attention for its involvement in apoptosis, cell growth, and cytokine release. Recent studies showed that P2X(7) is overexpressed in chronic lymphocytic leukemia and breast and prostate cancer.

Stimulation of purinergic receptors modulates chemokine expression in human keratinocytes.

ATP is abundantly released from stressed or damaged cells in response to mechanical stimulation, bacteria, or noxious agents. In this study, we have investigated the possible involvement of P2 receptors (receptor for extracellular nucleotides) in the expression and release of inflammatory mediators by human keratinocytes. Notably, extracellular ATP displayed a complex regulation of IFN-gamma-stimulated chemokine expression, with upregulation of CC chemokine ligand 2 (CCL2), CCL5 and CXC chemokine ligand 8 (CXCL8), and suppression of the receptor CXC chemokine receptor 3 (CXCR3), CXCL9, CXCL10, and CXCL11.

The extracellular nucleotide UTP is a potent inducer of hematopoietic stem cell migration.

Homing and engraftment of hematopoietic stem cells (HSCs) to the bone marrow (BM) involve a complex interplay between chemokines, cytokines, and nonpeptide molecules. Extracellular nucleotides and their cognate P2 receptors are emerging as key factors of inflammation and related chemotactic responses. In this study, we investigated the activity of extracellular adenosine triphosphate (ATP) and uridine triphosphate (UTP) on CXCL12-stimulated CD34+ HSC chemotaxis.

Extracellular adenosine 5'-triphosphate modulates interleukin-6 production by human thyrocytes through functional purinergic P2 receptors.

We investigated the presence of P2 receptors (P2Rs) in human thyrocytes and their possible involvement in the modulation of cytokine release. P2Rs expression was assessed by RT-PCR and, when possible, by immunoblotting. Human primary thyrocytes express the mRNA for the following P2X and P2Y subtypes: P2X(3), P2X(5), P2X(6), P2X(7), and P2Y(1), P2Y(2), P2Y(4), and P2Y(11).