CD11B CD18 (MAC-1) IS REQUIRED FOR DEGRANULATION OF HUMAN EOSINOPHILSINDUCED BY HUMAN RECOMBINANT CRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND PLATELET-ACTIVATING-FACTOR/

Recent evidence suggests adhesion molecules play an important role in the function of leukocytes. Because human eosinophils are known to exp ress beta 2 integrins, we hypothesized that these adhesion molecules m ediate the effector function of eosinophils. Normal human eosinophils incubated in albumin-coated polystyrene plates released granule protei n and produced superoxide anion when stimulated with human recombinant granulocyte-macrophage CSF (rGM-CSF), platelet-activating factor (PAF ), or PMA. Simultaneous monitoring of eosinophil adhesion and degranul ation showed that degranulation was always preceded by cellular adhesi on regardless of stimuli. Furthermore, eosinophil degranulation induce d by human rGM-CSF and PAF was abolished in suspension culture of the cells when the cell suspensions were gently stirred. To identify the m olecules involved in this adhesion-dependent degranulation, we have in vestigated the effects of mAbs (mAb) against beta 2 integrins. mAb rea ctive with CD18 markedly inhibited the eosinophil adhesion and degranu lation induced by PAF and human rGM-CSF. mAb reactive with CD11b also moderately inhibited the adhesion and degranulation. In contrast, mAb reactive with CD11a slightly enhanced or showed no effect on the adhes ion and degranulation by human rGM-CSF or PAF. Superoxide production i nduced by human rGM-CSF and PAF was also abolished by the treatment of cells with anti-CD18 mAb. mAb against CD11b and CD18 had little effec t on degranulation and superoxide production induced by PMA. These res ults indicate that CD11b/CD18 (Mac-1)-dependent cellular adhesion play s an important role in the degranulation and superoxide production of eosinophils induced by human rGM-CSF and PAF, and that these mechanism s may be employed in vivo where eosinophils contact with stromal cells and/or proteins.