Disease relevance of Nt5e

• Crucial role for ecto-5'-nucleotidase (CD73) in vascular leakage during hypoxia [1].
• CD73(-/-) mice challenged with bleomycin exhibited enhanced pulmonary inflammation and fibrosis as well as exaggerated expression of proinflammatory and profibrotic mediators in the lung [2].
• These data suggested that in the Ig-secreting B-cell lymphoma lines, there was an association between the inducibility of 5'-NT and the capacity of these cell lines to undergo plasma-cytoid-like transformation in response to TPA [3].
• In neuroblastoma cells, estrogen increases cAMP and the phosphorylation of the cAMP response element-binding protein in a time frame that precedes induction of NT/N gene transcription [4].
• Ecto-5'-nucleotidase expression during human B cell development. An explanation for the heterogeneity in B lymphocyte ecto-5'-nucleotidase activity in patients with hypogammaglobulinemia [5].

High impact information on Nt5e

• Murine CD1 has been implicated in the development and function of an unusual subset of T cells, termed natural T (NT) cells, that coexpress the T cell receptor (TCR) and the natural killer cell receptor NK1 [6].
• NT cell numbers in the thymus, spleen, and liver of these mice were dramatically reduced [6].
• The generation of extracellular adenosine involves phosphohydrolysis of adenine nucleotide intermediates, and is regulated by the terminal enzymatic step catalyzed by ecto-5'-nucleotidase (CD73) [1].
• Ecto-5'-nucleotidase is known to be diminished markedly in activated compared to control mouse macrophages [7].
• We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5'NT/CD73-mediated dephosphorylation of 5'-AMP, presumably generated from released ATP [8].

Chemical compound and disease context of Nt5e

• The increase of ecto-5'-nucleotidase in heart myocytes from infected mice may produce cardioprotective adenosine that may be independent of beta-adrenergic function, based on the hypoperfusion conditions of acute chagasic cardiomyopathy [9].

Biological context of Nt5e

• Murine ecto-5'-nucleotidase (CD73): cDNA cloning and tissue distribution [10].
• To investigate the role of adenosine formed extracellularly in vascular homeostasis, mice with a targeted deletion of the cd73/ecto-5'-nucleotidase were generated [11].
• Thus, our data provide the first evidence that adenosine, extracellularly formed by CD73, can modulate coronary vascular tone, inhibit platelet activation, and play an important role in leukocyte adhesion to the vascular endothelium in vivo [11].
• Second, there is no methotrexate-mediated increase in extracellular adenosine concentration in the supernate of cells deficient in ecto-5'-nucleotidase, but there is a marked increase in extracellular adenosine concentration in the supernates of these cells after transfection and surface expression of the enzyme [12].
• Expression of the neurotensin/neuromedin (NT/N) gene in preoptic area neurons is dramatically enhanced by estrogen in vivo, even though its promoter lacks palindromic estrogen response elements [4].

Anatomical context of Nt5e

• CD73 and Ly-6A/E distinguish in vivo primed but uncommitted mouse CD4 T cells from type 1 or type 2 effector cells [13].
• CD73+ Ly6A/E- memory CD4 T cells were identified in normal C57BL/6 mice, and the proportion of these cells was highest in lymph nodes, lower in spleens, and lowest in the lungs [13].
• Immunohistochemistry revealed strong CD73 expression on the endothelium of conduit vessels in wild-type (WT) mice [11].
• Neither Ig secretion nor 5'-NT activity was induced by TPA in any of 4 nonsecreting cell lines studied [3].
• First, pretreatment of a human microvascular endothelial cell line (HMEC-1) with methotrexate increases extracellular adenosine after exposure of the pretreated cells to activated neutrophils; the ecto-5'-nucleotidase inhibitor alpha, beta-methylene adenosine-5'-diphosphate (APCP) abrogates completely the increase in extracellular adenosine [12].

Associations of Nt5e with chemical compounds

• Guided by previous work indicating that hypoxia-induced vascular leakage is, at least in part, controlled by adenosine, we generated mice with a targeted disruption of the third coding exon of Cd73 to test the hypothesis that CD73-generated extracellular adenosine functions in an innate protective pathway for hypoxia-induced vascular leakage [1].
• CD73(+/+) animals challenged with bleomycin and supplemented with exogenous nucleotidase also exhibited reduced inflammation [2].
• The murine cDNA, encoding the purine catabolic enzyme, ecto-5'-nucleotidase (NT), was cloned and the tissue-specific distribution of both the mRNA and enzyme activity was examined [10].
• To identify the source(s) of extracellular adenosine, we examined the effects of dipyridamole, an inhibitor of nucleoside transport, and alpha,beta-methyleneadenosine 5'-diphosphate (AOPCP), an inhibitor of ecto-5'-nucleotidase, on AVP-stimulated IscCl [14].
• The results of the experiments reported here provide three distinct lines of evidence that adenosine results from the ecto-5'-nucleotidase- mediated conversion of adenine nucleotides to adenosine [12].
• We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation [15].
• The A(2B) receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha [16].

Other interactions of Nt5e

• Because rat peritoneal macrophages exhibit a particular binding capacity to rat glomerular mesangial cells in vitro, we have studied the effect of macrophages on two plasma membrane enzymes, ecto-5'-nucleotidase and ecto-Mg2+ ATPase, or rat cultured mesangial cells [17].
• Alterations observed in the interstitial fibroblast-like cells included an increased number and complexity of cellular processes, enhanced expression of contractile elements, particularly of the intermediate filament desmin, and reduced expression of ecto-5'-nucleotidase [18].
• The periimplantation adenosine surge coincided with uterine expression of 5'-NT, an enzyme which catalyzes the irreversible dephosphorylation of 5'-AMP to adenosine [19].
• The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryo-decidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5'-nucleotidase (5'-NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4) [19].

Analytical, diagnostic and therapeutic context of Nt5e

• Using flow cytometry, we have demonstrated a distinct population of V alpha24+, V beta11+, CD56+ T cells consistent with NT cells [20].
• A marked increase of ecto-5'-nucleotidase activity was observed in cocultures of rat mesangial cells and peritoneal macrophages [17].
• We conclude that Ly-6C+ NT cells play a role in immunosurveillance against NK-sensitive as well as NK-resistant tumours in certain strains of mice [21].
• Mouse peritoneal macrophages elicited by intraperitoneal injection of sodium caseinate exhibit low levels of ecto-5'-nucleotidase (E. C. 3.1.3.5) activity in contrast to macrophages obtained by peritoneal lavage [22].
• The identification of a single RT-PCR product suggested that active and inactive eNT arise from the same mRNA and are generated by a differential post-translational processing [23].

References