Synergistic Activation of Eosinophil Superoxide Anion Generation by VCAM-1 and GM-CSF

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.