THE GM-CSF ANALOG E21R INDUCES APOPTOSIS OF NORMAL AND ACTIVATED EOSINOPHILS

There is evidence that eosinophils have an important role in the patho genesis of allergy and asthma. These cells are regulated by two classe s of polypeptides, the colony-stimulating factors, such as granulocyte -macrophage colony-stimulating factor (GM-CSF), and the chemokines, su ch as RANTES and eotaxin. GM-CSF is involved in the production, surviv al, and functional activation of eosinophils. RANTES and eotaxin regul ate the migration of eosinophils to inflammatory sites, but any effect of these chemokines on eosinophil survival is not known. In this stud y we demonstrate that although GM-CSF promoted eosinophil survival, th e specific GM-CSF analogue E21R induced apoptosis of eosinophils. Apop tosis was observed with unstimulated as well as with chemokine (RANTES and eotaxin)activated eosinophils. Neither RANTES nor eotaxin support ed eosinophil survival, and a RANTES antagonist did not affect either cell survival or apoptosis. E21R also induced apoptosis of eosinophils from asthmatic patients. These findings suggest that the GM-CSF recep tor may actively control the death as well as the survival of eosinoph ils, and thus precisely regulate their numbers and activities. Our dat a also indicate that chemokines are not involved in regulating the lif espan of eosinophils. The introduction of the GM-CSF analogue E21R may offer a novel therapy in inflammatory diseases associated with eosino phil infiltration of different etiologies.