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This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-101097v1 22/9/3276    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kreth, S. Articles by Thiel, M. PubMed PubMed Citation Articles by Kreth, S. Articles by Thiel, M.

Differential expression of 5'-UTR splice variants of the adenosine A_2A receptor gene in human granulocytes: identification, characterization, and functional impact on activation

Department of Anaesthesiology, Ludwig Maximilians University of Munich, Germany

¹ Correspondence: Clinic of Anaesthesiology, Klinikum Grosshadern, Marchioninistr. 15, D-81375 Munich, Germany. E-mail: mthiel{at}med.uni-muenchen.de

A key step in the pathogenesis of sepsis is the excessive and uncontrolled activation of polymorphonuclear neutrophils (PMNs). An inflammation-controlling function of adenosine receptors has been presumed; however, their role in PMN of sepsis patients is poorly defined. We investigated the expression of adenosine receptors in resting and lipopolysaccharide (LPS) -activated human PMNs, and in PMNs of sepsis patients. Our studies revealed that native human PMNs express almost equal distributions of all four adenosine receptor subtype transcripts, whereas exclusively the A_2A receptor (A_2AR) was up-regulated in LPS-stimulated PMNs and PMNs of sepsis patients. As a possible mechanism, we identified and fully characterized eight 5'-untranslated region (UTR) splice variants of the A_2AR gene resulting from alternative transcription and/or splicing of five noncoding exons. We report a differential, activation state-specific expression of 5'-UTR variants within the same cell type, indicating a new mechanism to modulate gene expression: In resting human PMNs, mainly A_2AR transcripts with long 5'-UTRs are expressed, whereas in stimulated PMNs and PMNs of septic patients, short 5'-UTRs predominate. Transcripts with short 5'-UTRs are more efficiently translated into protein. The correlation between changes of transcript patterns and A_2AR up-regulation offers interesting clues regarding the course of sepsis.—Kreth, S., Ledderose, C., Kaufmann, I., Groeger, G., Thiel, M. Differential expression of 5'-UTR splice variants of the adenosine A_2AR gene in human granulocytes: identification, characterization, and functional impact on activation.

Key Words: sepsis • 5'-untranslated region • alternative transcripts