Apoptosis in human eosinophils. Programmed cell death in the eosinophil leads to phagocytosis by macrophages and is modulated by IL-5.
Eosinophils are believed to injure tissues in a variety of allergic disease by virtue of their highly histotoxic contents and metabolites. They are readily observed in tissues during the allergic response yet the mechanisms governing the duration of tissue residence and route of removal remain obscure. We have previously reported in vitro and in vivo evidence that neutrophils undergo apoptosis (programmed cell death) and are recognized and ingested as intact cells by macrophages. We report that eosinophils, purified from the peripheral blood of asymptomatic healthy atopics, undergo apoptosis in vitro. After 72 to 96 h in culture, 57.0 +/- 6.2% (mean +/- SE) of the eosinophil population showed characteristic morphologic changes of apoptosis. Electrophoresis of the DNA from these cells demonstrated the typical "ladder" pattern of internucleosomal DNA cleavage, the hallmark of apoptosis-associated endonuclease activation. The rate of eosinophil apoptosis, slower than that reported for neutrophils, was delayed (by 80 +/- 6 h) in the presence of recombinant human IL-5, a cytokine previously reported to prolong eosinophil life in vitro but not known to modulate apoptosis. Aged, apoptotic eosinophils, but not fresh or aged preapoptotic eosinophils, were recognized and ingested as intact cells by macrophages. Apoptosis and ingestion by macrophages may represent a mechanism whereby the tissue longevity and removal of eosinophils is controlled.
Stern
M
M
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Meagher
L
L
Savill
J
J
Haslett
C
C
D016923:Cell Death; D002478:Cells, Cultured; D016922:Cellular Senescence; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D010587:Phagocytosis
D015848:Interleukin-5; D004706:Endodeoxyribonucleases