Linked Life Data

16177079

Source:http://linkedlifedata.com/resource/pubmed/id/16177079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-9-22
pubmed:abstractText
The effect of adenosine and its analogues on the cytotoxic activity of IL-2-activated NK cells was investigated. Adenosine is an endogenous ligand for four different adenosine receptor (AdoR) subtypes (AdoRA1, AdoRA2A, AdoRA2B, and AdoRA3). Increased concentrations of adenosine were found in ascites of MethA sarcoma or in culture medium of 3LL Lewis lung carcinoma growing under hypoxic conditions. We hypothesize that intratumor adenosine impairs the ability of lymphokine-activated killer (LAK) cells to kill tumor cells. The effect of AdoR engagement on LAK cells cytotoxic activity was analyzed using AdoR agonists and antagonists as well as LAK cells generated from AdoR knockout mice. Adenosine and its analogues efficiently inhibited the cytotoxic activity of LAK cells. CGS21680 (AdoRA2A agonist) and 5-N-ethylcarboxamide adenosine (NECA) (AdoRA2A/ADoRA2B agonist) inhibited LAK cell cytotoxicity in parallel with their ability to increase cAMP production. The inhibitory effects of stable adenosine analog 2-chloroadenosine (CADO) and AdoRA2 agonists were blocked by AdoRA2 antagonist ZM 241385. Adenosine and its analogues impair LAK cell function by interfering with both perforin-mediated and Fas ligand-mediated killing pathways. Studies with LAK cells generated from AdoRA1-/- and AdoRA3-/- mice ruled out any involvement of these AdoRs in the inhibitory effects of adenosine. LAK cells with genetically disrupted AdoRA2A were resistant to the inhibitory effects of adenosine, CADO and NECA. However, with extremely high concentrations of CADO or NECA, mild inhibition of LAK cytotoxicity was observed that was probably mediated via AdoRA2B signaling. Thus, by using pharmacological and genetic blockage of AdoRs, our results clearly indicate the prime importance of cAMP elevating AdoR2A in the inhibitory effect of adenosine on LAK cell cytotoxicity. The elevated intratumor levels of adenosine might inhibit the antitumor effects of activated NK cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4383-91
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16177079-2-Chloroadenosine, pubmed-meshheading:16177079-Adenosine, pubmed-meshheading:16177079-Adenosine-5'-(N-ethylcarboxamide), pubmed-meshheading:16177079-Animals, pubmed-meshheading:16177079-Carcinoma, Lewis Lung, pubmed-meshheading:16177079-Cell Line, Tumor, pubmed-meshheading:16177079-Cyclic AMP, pubmed-meshheading:16177079-Cytotoxicity, Immunologic, pubmed-meshheading:16177079-Fas Ligand Protein, pubmed-meshheading:16177079-Female, pubmed-meshheading:16177079-GTP-Binding Protein alpha Subunits, Gs, pubmed-meshheading:16177079-Killer Cells, Lymphokine-Activated, pubmed-meshheading:16177079-Killer Cells, Natural, pubmed-meshheading:16177079-Lymphocyte Activation, pubmed-meshheading:16177079-Membrane Glycoproteins, pubmed-meshheading:16177079-Mice, pubmed-meshheading:16177079-Mice, Inbred C57BL, pubmed-meshheading:16177079-Mice, Knockout, pubmed-meshheading:16177079-Purinergic P1 Receptor Agonists, pubmed-meshheading:16177079-Receptors, Purinergic P1, pubmed-meshheading:16177079-Signal Transduction
pubmed:year
2005
pubmed:articleTitle
Gs protein-coupled adenosine receptor signaling and lytic function of activated NK cells.
pubmed:affiliation
Department of Pathology and University of Pittsburgh Cancer Institute, University of Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural