Apoptotic response of eosinophils in chronic eosinophilic pneumonia.
To clarify the pathogenesis of chronic eosinophilic pneumonia (CEP), the apoptosis of eosinophils from bronchoalveolar lavage (BAL-Eos) was compared with that of eosinophils from peripheral blood (PB-Eos) in six cases of CEP. The survival rate of eosinophils and the percentage of apoptotic cells of both types of eosinophils were examined, and the effects of interleukin 5 (IL-5) were evaluated. The role of Fas expression in apoptosis of these eosinophils was also studied. The survival rate of BAL-Eos on the third day of culture was significantly higher than that of PB-Eos (p < 0.01). This was associated with a lower proportion of apoptotic cells in BAL-Eos than in PB-Eos; the percentages of apoptotic cells in PB-Eos and BAL-Eos after 24 h of incubation were 21.7 +/- 3.4% and 10.6 +/- 1.7% respectively. IL-5 suppressed apoptosis and increased the survival rate of both PB-Eos and BAL-Eos. It was found that the apoptotic character of BAL-Eos differed from that of PB-Eos in at least three ways. Firstly, the positive rate of Fas expression on PB-Eos was increased after 24 h of incubation, whereas that on BAL-Eos did not change. Secondly, the expression of Fas on PB-Eos was suppressed by IL-5 (18.5 +/- 4.2% - 8.3 +/- 3.2%, p < 0.05), whereas IL-5 failed to suppress Fas expression on BAL-Eos (3.3 +/- 1.6% - 3.6 +/- 1.0%). Lastly, binding of antibody to Fas antigen induced apoptosis of PB-Eos, but not of BAL-Eos. These data suggested that Fas seemed to be involved in the apoptosis of PB-Eos, whereas BAL-Eos were Fas-resistant in chronic eosinophilic pneumonia. In conclusion, apoptosis of eosinophils might be suppressed by proinflammatory cytokines such as IL-5 leading to their accumulation in the lung. Chronic stimulation of eosinophils in the alveolar space with IL-5 may play a crucial role chronic eosinophilic disorders.
Saita
N
N
First Dept of Internal Medicine, Kumamoto University, School of Medicine, Japan.
Yamanaka
T
T
Kohrogi
H
H
Ando
M
M
Hirashima
M
M
D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D004804:Eosinophils / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D019014:fas Receptor / Q000378:metabolism
D015848:Interleukin-5; D019014:fas Receptor