Eosinophil hematopoietins antagonize the programmed cell death of eosinophils. Cytokine and glucocorticoid effects on eosinophils maintained by endothelial cell-conditioned medium.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with IL-1 alpha (5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM (P less than 0.05). Dexamethasone (100 nM) decreased the constitutive GM-CSF elaboration by 49% (P less than 0.001) but did not diminish production by IL-1 alpha-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-1 alpha-stimulated endothelial cell-conditioned medium (P less than 0.05), which suggested viability antagonism by glucocorticoids. After 24 h of culture, eosinophil viability for replicate cells in enriched medium alone or with 1 pM GM-CSF decreased from means of 43 and 75% to means of 21 and 54%, respectively, when dexamethasone was included (P less than 0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonuclease-specific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathobiologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentrations that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of select eosinophilic disorders to glucocorticoids.
Her
E
E
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Frazer
J
J
Austen
K F
KF
Owen
W F
WF
D002470:Cell Survival / Q000187:drug effects*; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology
D003470:Culture Media; D016207:Cytokines; D007375:Interleukin-1; D007377:Interleukin-3; D015848:Interleukin-5; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA