In:
International Archives of Allergy and Immunology, S. Karger AG, Vol. 133, No. 4 ( 2004), p. 357-364
Abstract:
〈 i 〉 Background: 〈 /i 〉 Eosinophils are important cells in host immunity to infections by parasitic worms. Tissue-invasive helminthic parasites have been known to induce apoptosis of immune cells for their successful establishment in vivo. We have previously found that high doses of excretory-secreted products (ESP) secreted by lung fluke 〈 i 〉 Paragonimus westermani 〈 /i 〉 newly excysted metacercariae (PwNEM), which cause pulmonary or extrapulmonary paragonimiasis in human beings, accelerate eosinophil cell death. However, little is known about the mechanism of eosinophil apoptosis induced by the 〈 i 〉 Paragonimus 〈 /i 〉 -derived products. 〈 i 〉 Objective: 〈 /i 〉 We examined involvement of caspase 3 activation in eosinophil cell death induced by ESP produced by PwNEM. 〈 i 〉 Methods: 〈 /i 〉 Eosinophils were isolated from the peripheral blood of healthy donors by CD16-negative immunomagnetic selection. We examined the inhibitory effect of pan-caspase inhibitor on ESP-triggered phosphatidylserine (PS) externalization on the outer surface of eosinophils and intracellular activation of caspase 3 in cell lysates treated with the ESP. 〈 i 〉 Results: 〈 /i 〉 When ESP secreted by PwNEM were incubated for up to 3 h with eosinophils, they increased surface exposure of PS on eosinophils in a time- and dose-dependent manner. This proapoptotic effect of the ESP on eosinophils was significantly inhibited by pretreatment of cells with pan-caspase inhibitor z-VAD-fmk, and was completely abolished by heat inactivation of ESP at 56°C. The activated forms of caspase 3 were also clearly detected in eosinophils incubated with ESP. Moreover, ESP potently inhibited prolonged survival of eosinophils induced by cytokines such as IL-5, IL-3, and GM-CSF. 〈 i 〉 Conclusion: 〈 /i 〉 These results suggest that ESP secreted by PwNEM contain biological active factors causing caspase-3-mediated apoptosis of human eosinophils, thereby enabling the larvae to evade and to subvert the tackle by eosinophils during the early phase of the infection.
Type of Medium:
Online Resource
ISSN:
1018-2438
,
1423-0097
Language:
English
Publisher:
S. Karger AG
Publication Date:
2004
detail.hit.zdb_id:
1482722-0
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