SYNERGISTIC ACTIVATION OF EOSINOPHIL SUPEROXIDE ANION GENERATION BY VCAM-1 AND GM-CSF - INVOLVEMENT OF TYROSINE KINASE AND PROTEIN-KINASE-C

During the development of allergic inflammation of asthma, eosinophils (EOS) are likely to interact with endothelial adhesion molecules, suc h as VCAM-1 and inflammatory cytokines, such as GM-CSF. To determine w hether VCAM-1 and GM-CSF can interact to modify EOS superoxide anion ( OZ) generation, peripheral blood EOS were incubated in either recombin ant 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 synergi stically to stimulate O-2(-) generation which was significantly inhibi ted by either genistein, a tyrosine kinase inhibitor, or staurosporine , a protein kinase C inhibitor. These results indicate that interactio n between VCAM-1 and GM-CSF can stimulate EOS function and its eventua l contribution to the allergic inflammation process. Furthermore, our results demonstrate the involvement of tyrosine kinase and protein kin ase C in this specific EOS activation.