The GM-CSF analogue E21R induces apoptosis of normal and activated eosinophils.
There is evidence that eosinophils have an important role in the pathogenesis of allergy and asthma. These cells are regulated by two classes of polypeptides, the colony-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), and the chemokines, such as RANTES and eotaxin. GM-CSF is involved in the production, survival, and functional activation of eosinophils. RANTES and eotaxin regulate the migration of eosinophils to inflammatory sites, but any effect of these chemokines on eosinophil survival is not known. In this study we demonstrate that although GM-CSF promoted eosinophil survival, the specific GM-CSF analogue E21R induced apoptosis of eosinophils. Apoptosis was observed with unstimulated as well as with chemokine (RANTES and eotaxin)-activated eosinophils. Neither RANTES nor eotaxin supported 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 receptor may actively control the death as well as the survival of eosinophils, and thus precisely regulate their numbers and activities. Our data also indicate that chemokines are not involved in regulating the lifespan of eosinophils. The introduction of the GM-CSF analogue E21R may offer a novel therapy in inflammatory diseases associated with eosinophil infiltration of different etiologies.
Iversen
P O
PO
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, Australia.
Robinson
D
D
Ying
S
S
Meng
Q
Q
Kay
A B
AB
Clark-Lewis
I
I
Lopez
A F
AF
D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000503:physiopathology; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000494:pharmacology; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D047091:Eosinophil Granule Proteins; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D010544:Peroxidases / Q000378:metabolism; D011994:Recombinant Proteins; D012260:Ribonucleases
D001798:Blood Proteins; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D011994:Recombinant Proteins; C101659:granulocyte-macrophage colony-stimulating factor, Arg(21)-; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D012260:Ribonucleases