Inosine stimulates chemotaxis, Ca2+-transients and actin polymerization in immature human dendritic cells via a pertussis toxin-sensitive mechanism independent of adenosine receptors.
Inosine is an endogenous purine nucleoside, which is formed by adenosine deaminidase during adenosine breakdown and is released into the extracellular space from the sympathetic nervous system or injured cells. Here, we studied the biological activity of inosine on human dendritic cells (DC), which are specialized antigen presenting cells characterized by their ability to migrate from the blood to peripheral tissues, and then to secondary lymphoid organs where they initiate adaptive immune responses. In immature DC, inosine concentration-dependently stimulated Ca(2+)-transients, actin polymerization, and chemotaxis. Experiments with adenosine receptor antagonists and pertussis toxin (PTX) as well as desensitization studies suggested that the activity of inosine was mediated by a G protein-coupled receptor pathway independent of adenosine receptors. DC, induced to mature by lipopolysaccharide, lost their ability to respond towards inosine with these activities. Moreover, inosine did neither influence membrane expression of CD54, CD80, CD83, CD86, HLA-DR, and MHC class I molecules nor modulated secretion of interleukin (IL)-12, IL-10, and tumor necrosis factor alpha in immature and lipopolysaccharide-matured DC. In aggregate, our study indicates that inosine may be involved in the trafficking control system of immature DC, and mediates its chemotactic activity by a PTX-sensitive mechanism independent of adenosine receptors.
Department of Pneumology, University of Freiburg, Germany.
Marco
M
Idzko
Elisabeth
E
Panther
Hinrich C
HC
Bremer
Wolfram
W
Windisch
Stephan
S
Sorichter
Yared
Y
Herouy
Peter
P
Elsner
Maja
M
Mockenhaupt
Giampiero
G
Girolomoni
Johannes
J
Norgauer
D000199:Actins / Q000187:drug effects*; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007288:Inosine / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C110041:9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline; D000199:Actins; D015703:Antigens, CD; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D058915:Purinergic P1 Receptor Antagonists; D011799:Quinazolines; D018047:Receptors, Purinergic P1; D014230:Triazoles; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; D007288:Inosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D037342:Pertussis Toxin; D002118:Calcium