title: Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation: Ca(++) mobilization and actin reorganization in human eosinophils.
abstract: Eosinophils are major effector cells in cellular inflammatory conditions such as parasitic infections, atopic diseases, bullous dermatoses, and vasculitis. Biological activities of adenosine triphosphate (ATP) were characterized in human eosinophils and compared with those of other eosinophil activators such as complement fragment product C5a, platelet-activating factor (PAF), and eotaxin. ATP initiated production of reactive oxygen metabolites, as demonstrated by lucigenin-dependent chemiluminescence. Furthermore, ATP caused up-regulation of the integrin CD11b. In addition, fluorescence microscope measurements labeled with fura-2 (1-[2-(5-carboxy-oxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2' -amino-5' -methyl-phenoxy)-ethane-N, N, N, N'-tetraacetic acid, pentaacetoxymethyl ester) eosinophils in the presence or absence of ethyleneglycotetraacetic acid (EGTA) indicated that there was Ca(++) mobilization from intracellular stores by ATP. Flow cytometric studies showed transient actin polymerization upon stimulation with ATP and its stable analogues adenosine 5'-0-(3-thiotriphosphate) and 2-methylthioadenosine triphosphate tetrasodium (met-ATP). The reactions induced by ATP were comparable to those obtained by C5a, PAF, and eotaxin. Production of reactive oxygen metabolites and actin polymerization after stimulation with ATP was inhibited by pertussis toxin, which indicated involvement of receptor-coupled guanine nucleotide-binding proteins (G(i) proteins). In addition, experiments with oxidized ATP also suggest involvement of P2X receptors in this activation process. The results show that ATP is a strong activator of eosinophils and has biological activity comparable to those of the eosinophil chemotaxins C5a, PAF, and eotaxin. The findings strongly suggest a role of ATP in the pathogenesis of eosinophilic inflammation as an activator of proinflammatory effector functions.
authors.affiliation: Department of Dermatology, University of Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dichmann
authors.forename: M
authors.initials: M
authors.lastname: Idzko
authors.forename: U
authors.initials: U
authors.lastname: Zimpfer
authors.forename: C
authors.initials: C
authors.lastname: Hofmann
authors.forename: D
authors.initials: D
authors.lastname: Ferrari
authors.forename: W
authors.initials: W
authors.lastname: Luttmann
authors.forename: C
authors.initials: C
authors.lastname: Virchow
authors.forename: F
authors.initials: F
authors.lastname: Di Virgilio
authors.forename: J
authors.initials: J
authors.lastname: Norgauer
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D020013:Calcium Signaling; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015936:Complement C5a / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004533:Egtazic Acid / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D005609:Free Radicals; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000502:physiology; D016897:Respiratory Burst; D013873:Thionucleotides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000199:Actins; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D005609:Free Radicals; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; C022571:adenosine 5'-O-(3-thiotriphosphate); D004533:Egtazic Acid; D015936:Complement C5a; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D016257:Fura-2; C008501:2-methylthio-ATP