Adenosine triphosphate-induced oxygen radical production and CD11b up-regulation: Ca(++) mobilization and actin reorganization in human eosinophils.

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.

[1]  D. Ferrari,et al.  Cytolytic P2X purinoceptors , 1998, Cell Death and Differentiation.

[2]  J. Norgauer,et al.  The Monocyte Chemotactic Protein-4 Induces Oxygen Radical Production, Actin Reorganization, and CD11b Up-regulation via a Pertussis Toxin-Sensitive G-Protein in Human Eosinophils☆☆☆ , 1997 .

[3]  F. Di Virgilio,et al.  Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. , 1997, Journal of immunology.

[4]  C. Kennedy,et al.  Neuronal release of soluble nucleotidases and their role in neurotransmitter inactivation , 1997, nature.

[5]  D. Ferrari,et al.  Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin , 1997, The Journal of experimental medicine.

[6]  D. Candinas,et al.  Loss of ATP Diphosphohydrolase Activity with Endothelial Cell Activation , 1997, The Journal of experimental medicine.

[7]  D. Ferrari,et al.  Purinoceptor function in the immune system , 1996 .

[8]  H. Zimmermann,et al.  Extracellular purine metabolism , 1996 .

[9]  J. Norgauer,et al.  Recombinant human eotaxin induces oxygen radical production, Ca(2+)-mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein. , 1996, Blood.

[10]  Y. Kakeji,et al.  RSR13: Effects on tumor oxygenation and response to therapy , 1996 .

[11]  G. Burnstock,et al.  Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells , 1996, Trends in Neurosciences.

[12]  F. Virgilio.  The P2Z purinoceptor: an intriguing role in immunity, inflammation and cell death , 1995 .

[13]  G. Cutting,et al.  CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP , 1995, Cell.

[14]  C. Dahinden,et al.  Basophil and eosinophil activation by CC chemokines. , 1995, International archives of allergy and immunology.

[15]  P. Bruijnzeel.  Eosinophil Tissue Mobilization in Allergic Disorders , 1994, Annals of the New York Academy of Sciences.

[16]  M. Oppermann,et al.  C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. , 1994, Blood.

[17]  M. Baggiolini,et al.  CC chemokines in allergic inflammation. , 1994, Immunology today.

[18]  M. Oppermann,et al.  C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils , 1994, European journal of immunology.

[19]  M. Camps,et al.  Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits , 1992, Nature.

[20]  A. B. Kay,et al.  "Helper" (CD4+) T cells and eosinophils in allergy and asthma. , 1992, The American review of respiratory disease.

[21]  K. Blaser,et al.  Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. , 1991, The Journal of allergy and clinical immunology.

[22]  A. Mantovani,et al.  The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine. , 1991, Journal of immunology.

[23]  Melvin Berger,et al.  Chronic Treatment With P2‐Purinergic Receptor Agonists Induces Phenotypic Modulation of the HL‐60 and U937 Human Myelogenous Leukemia Cell Lines , 1991, Journal of leukocyte biology.

[24]  A. Cohen,et al.  ATP-induced activation of human B lymphocytes via P2-purinoceptors. , 1991, Journal of immunology.

[25]  M. Sitkovsky,et al.  Extracellular ATP in T-lymphocyte activation: possible role in effector functions. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Colman.  Aggregin: a platelet ADP receptor that mediates activation , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[27]  K. Jakobs,et al.  Two distinct Gi-proteins mediate formyl peptide receptor signal transduction in human leukemia (HL-60) cells. , 1989, The Journal of biological chemistry.

[28]  T. Stossel,et al.  From signal to pseudopod. How cells control cytoplasmic actin assembly. , 1989, The Journal of biological chemistry.

[29]  R. Berne,et al.  The cardiac effects of adenosine. , 1989, Progress in cardiovascular diseases.

[30]  P. Ward,et al.  Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[31]  A. Wardlaw,et al.  Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. , 1986, The Journal of clinical investigation.

[32]  A. Jesaitis,et al.  Signal transduction and ligand-receptor dynamics in the human neutrophil. Transient responses and occupancy-response relations at the formyl peptide receptor. , 1985, The Journal of biological chemistry.

[33]  E. Goetzl,et al.  Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products. , 1982, Clinical and experimental immunology.

[34]  B. Gomperts,et al.  The ATP4- receptor of rat mast cells. , 1980, The Biochemical journal.

[35]  J. Pearson,et al.  Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides , 1979, Nature.

[36]  S. Gregory,et al.  Adenosine and adenine nucleotides are mitogenic for mouse thymocytes. , 1978, Biochemical and biophysical research communications.

[37]  R. Arceci,et al.  The multidrug resistance (mdr1) gene product functions as an ATP channel. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  L. Koenderman,et al.  Human platelets secrete chemotactic activity for eosinophils , 1993 .

[39]  M. Camps,et al.  Isozyme-selective stimulation of phospholipase C-beta 2 by G protein beta gamma-subunits. , 1992, Nature.