title: Synergistic activation of eosinophil superoxide anion generation by VCAM-1 and GM-CSF. Involvement of tyrosine kinase and protein kinase C.
abstract: During the development of allergic inflammation of asthma, eosinophils (EOS) are likely to interact with endothelial adhesion molecules, such as VCAM-1 and inflammatory cytokines, such as GM-CSF. To determine whether VCAM-1 and GM-CSF can interact to modify EOS superoxide anion (O2-) generation, peripheral blood EOS were incubated in either recombinant human (rh)-VCAM-1 or buffer (control)-coated 96-well plates in the presence or absence of 100 pM GM-CSF. VCAM-1 and GM-CSF acted synergistically to stimulate O2- generation which was significantly inhibited by either genistein, a tyrosine kinase inhibitor, or staurosporine, a protein kinase C inhibitor. These results indicate that interaction between VCAM-1 and GM-CSF can stimulate EOS function and its eventual contribution to the allergic inflammation process. Furthermore, our results demonstrate the involvement of tyrosine kinase and protein kinase C in this specific EOS activation.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: J B
authors.initials: JB
authors.lastname: Sedgwick
authors.forename: W W
authors.initials: WW
authors.lastname: Busse
mesh_terms: D001249:Asthma / Q000276:immunology; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D047428:Protein Kinase Inhibitors; D012220:Rhinitis / Q000276:immunology; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor