title: Activation of human alveolar macrophages via P2 receptors: coupling to intracellular Ca2+ increases and cytokine secretion.
abstract: Alveolar macrophages play a crucial role in the pathogenesis of inflammatory airway diseases. By the generation and release of different inflammatory mediators they contribute to both recruitment of different leukocytes into the lung and to airway remodeling. A potent stimulus for the release of inflammatory cytokines is ATP, which mediates its cellular effects through the interaction with different membrane receptors, belonging to the P2X and P2Y families. The aim of this study was to characterize the biological properties of purinoceptors in human alveolar macrophages obtained from bronchoalveolar lavages in the context of inflammatory airway diseases. The present study is the first showing that human alveolar macrophages express mRNA for different P2 subtypes, namely P2X(1), P2X(4), P2X(5), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(6), P2Y(11), P2Y(13), and P2Y(14). We also showed that extracellular ATP induced Ca(2+) transients and increased IL-1beta secretion via P2X receptors. Furthermore, extracellular nucleotides inhibited production of IL-12p40 and TNF-alpha, whereas IL-6 secretion was up-regulated. In summary, our data further support the hypothesis that purinoceptors are involved in the pathogenesis of inflammatory lung diseases.
authors.affiliation: University Hospital Freiburg, Department of Pneumology, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Myrtek
authors.forename: Tobias
authors.initials: T
authors.lastname: Müller
authors.forename: Verena
authors.initials: V
authors.lastname: Geyer
authors.forename: Natalie
authors.initials: N
authors.lastname: Derr
authors.forename: Davide
authors.initials: D
authors.lastname: Ferrari
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.forename: Thorsten
authors.initials: T
authors.lastname: Dürk
authors.forename: Stephan
authors.initials: S
authors.lastname: Sorichter
authors.forename: Werner
authors.initials: W
authors.lastname: Luttmann
authors.forename: Michael
authors.initials: M
authors.lastname: Kuepper
authors.forename: Johannes
authors.initials: J
authors.lastname: Norgauer
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: J Christian
authors.initials: JC
authors.lastname: Virchow
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D002118:Calcium