Search results for " A2"

Chronic myelogenous leukaemia exosomes modulate bone marrow microenvironment through activation of epidermal growth factor receptor

2016

Abstract Chronic myelogenous leukaemia (CML) is a clonal myeloproliferative disorder. Recent evidence indicates that altered crosstalk between CML and mesenchymal stromal cells may affect leukaemia survival; moreover, vesicles released by both tumour and non‐tumour cells into the microenvironment provide a suitable niche for cancer cell growth and survival. We previously demonstrated that leukaemic and stromal cells establish an exosome‐mediated bidirectional crosstalk leading to the production of IL8 in stromal cells, thus sustaining the survival of CML cells. Human cell lines used are LAMA84 (CML cells), HS5 (stromal cells) and bone marrow primary stromal cells; gene expression and protei…

Characterization of crustacyanin-A2 subunit as a component of the organic matrix of gastroliths from the crayfish Cherax quadricarinatus.

2009

AbstractLike the lobsters, some terrestrial crabs and other crayfishes, the Australian red claw crayfish, Cherax quadricarinatus, elaborates in its stomach wall calcium storage structures called gastroliths. For understanding the cyclic elaboration and stabilization of these amorphous calcified structures, we studied the organic matrix (OM) of these paired biomineralizations. After decalcification with acetic acid, we analysed the proteinaceous components of an acetic acid-insoluble fraction by two-dimensional electrophoresis. Nine spots were digested by trpsin and the tryptic peptides were sequenced by nanoLC-nanoESI-MS/MS mass spectrometry. About 100 peptidic sequences were compared to se…

2006

Prior studies demonstrate that adenosine, acting at one or more of its receptors, mediates the anti-inflammatory effects of methotrexate in animal models of both acute and chronic inflammation. Both adenosine A2A and A3 receptors contribute to the anti-inflammatory effects of methotrexate treatment in the air pouch model of inflammation, and the regulation of inflammation by these two receptors differs at the cellular level. Because different factors may regulate inflammation at different sites we examined the effect of low-dose weekly methotrexate treatment (0.75 mg/kg/week) in a model of acute peritoneal inflammation in adenosine A2A receptor knockout mice and A3 receptor knockout mice an…

Spontaneous domain formation of phospholipase A2 at interfaces: fluorescence microscopy of the interaction of phospholipase A2 with mixed monolayers …

1992

Abstract Fluorescence microscopy has recently been proven to be an ideal tool to investigated the specific interaction of phospholipase A 2 with oriented substrate monolayers. Using a dual labeling technique, it could be shown that phospholipase A 2 can specifically attack and hydrolyze solid analogous l -α-DPPC domains. After a critical extent of monolayer hydrolysis the enzyme itself starts to aggregate forming regular shaped protein domains (Grainger et al. (1990) Biochim. Biophys. Acta 1023. 365–379). In order to confirm that the existence of hydrolysis products in the mononlayer is necessary for the observed aggregation of phospholipase A 2 , mixed monolayers of d - and l -α-DPPC, l -α…

Endogenous peroxynitrite modulates PGHS-1–dependent thromboxane A2 formation and aggregation in human platelets

2008

Aggregation of activated platelets is considerably mediated by the autocrine action of thromboxane A2 (TxA2) which is formed in a prostaglandin endoperoxide H2 synthase-1 (PGHS-1 or COX-1)-dependent manner. The activity of PGHS-1 can be stimulated by peroxides, an effect termed "peroxide tone", that renders PGHS-1 the key regulatory enzyme in the formation of TxA2. Activated platelets release nitric oxide (*NO) and superoxide (O*2) but their interactions with the prostanoid pathway have been controversially discussed in platelet physiology and pathophysiology. The current study demonstrates that endogenously formed peroxynitrite at nanomolar concentrations, originating from the interaction …

CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death

2011

Abstract Extracellular adenosine (ADO), generated from ATP or ADP through the concerted action of the ectoenzymes CD39 and CD73, elicits autocrine and paracrine effects mediated by type 1 purinergic receptors. We have tested whether the expression of CD39 and CD73 by chronic lymphocytic leukemia (CLL) cells activates an adenosinergic axis affecting growth and survival. By immunohistochemistry, CD39 is widely expressed in CLL lymph nodes, whereas CD73 is restricted to proliferation centers. CD73 expression is highest on Ki-67+ CLL cells, adjacent to T lymphocytes, and is further localized to perivascular areas. CD39+/CD73+ CLL cells generate ADO from ADP in a time- and concentration-dependen…

Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway.

2014

Abstract Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC–Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC–Treg clusters, indicating a ro…

Increased thromboxane biosynthesis in type IIa hypercholesterolemia.

1992

BACKGROUND Increased platelet thromboxane (TX)A2 production has been described in type IIa hypercholesterolemia. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo, we studied the urinary excretion of its major enzymatic metabolites in 46 patients with type IIa hypercholesterolemia and 20 age-matched controls. METHODS AND RESULTS Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. The excretion rate of 11-dehydro-TXB2 was significantly (p less than 0.001) higher in patients (68.7 +/- 35.1 ng/hr, mean +/- SD) than in controls (22.4 +/- 9.4 ng/hr), with metabolite excretion greater tha…

Identification of KRT16 as a target of an autoantibody response in complex regional pain syndrome

2016

Abstract Objective Using a mouse model of complex regional pain syndrome (CRPS), our goal was to identify autoantigens in the skin of the affected limb. Methods A CRPS-like state was induced using the tibia fracture/cast immobilization model. Three weeks after fracture, hindpaw skin was homogenized, run on 2-d gels, and probed by sera from fracture and control mice. Spots of interest were analyzed by liquid chromatography-mass spectroscopy (LC-MS) and the list of targets validated by examining their abundance and subcellular localization. In order to measure the autoantigenicity of selected protein targets, we quantified the binding of IgM in control and fracture mice sera, as well as in co…

Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia

1995

Abstract Thromboxane A 2 (TXA 2 ) biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) was previously shown to reduce platelet aggregation and TXB 2 production ex vivo, we investigated TXA 2 biosynthesis and platelet function in 24 patients with type IIa hypercholesterolemia randomized to receive in a double-blind fashion simvastatin (20 mg/d) or placebo for 3 months. The urinary excretion of 11-dehydro-TXB 2 , largely a reflection of platelet TXA 2 production in vivo, was measured by a previously validated radioimmunoassay technique. Blood lipid levels and urinary 11-dehyd…