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Roles of Bcl-2 and caspase-9 and -3 in CD30-induced human eosinophil apoptosis

 Hye Jin Lee  ;  Eun-Kyoung Lee  ;  Young Eun Seo  ;  Youn Ho Shin  ;  Hwan Soo Kim  ;  Yoon Hong Chun  ;  Jong-Seo Yoon  ;  Hyun Hee Kim  ;  Man Yong Han  ;  Chang-Keun Kim  ;  Kyu-Earn Kim  ;  Young Yull Koh  ;  Jin Tack Kim 
 Journal of Microbiology, Immunology and Infection, Vol.50(2) : 145-152, 2017 
Journal Title
 Journal of Microbiology, Immunology and Infection 
Issue Date
Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/physiology* ; Apoptosis/immunology* ; Blotting, Western ; Caspase 3/physiology* ; Caspase 8/metabolism ; Caspase 9/physiology* ; Caspases ; Caspases, Initiator ; Cells, Cultured/drug effects ; Cells, Cultured/metabolism ; Eosinophils/cytology ; Eosinophils/immunology* ; Flow Cytometry ; Gene Expression ; Humans ; Interleukin-5/metabolism ; Ki-1 Antigen/biosynthesis ; Ki-1 Antigen/immunology* ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-bcl-2/physiology*
Bcl-2 ; apoptosis ; caspases ; eosinophils
BACKGROUND/PURPOSE: Activation of cell surface CD30 by immobilized anti-CD30 monoclonal antibodies (mAb) induces strong apoptosis in human eosinophils. This anti-CD30 mAb-induced eosinophil apoptosis is inhibited by the addition of inhibitors of p38, ERK1/2 mitogen-activated protein kinases, and phosphatidylinositol 3-kinase. However, there is little data investigating the role of Bcl-2 and caspases in eosinophil apoptosis induced by anti-CD30 mAb. We sought to determine whether anti-CD30 mAb induces human eosinophil apoptosis via Bcl-2 and caspase pathways. METHODS: Peripheral blood was drawn from 37 healthy volunteers. The CD30 expression on eosinophils was measured at various time points. Eosinophils were then cultured in plates precoated with anti-CD30 mAb (clone Ber-H8), isotype control immunoglobulin G1, interleukin (IL)-5, or dexamethasone. Western blot analysis was performed to determine the expression of Bcl-2, procaspase-8, -9, and -3, and caspase-8, -9, and -3 after cross-linking of CD30. Human eosinophils were also cultured in plates precoated with anti-CD30 mAb (clone Ber-H8) in the presence or absence of caspase-9 or -3 inhibitors. Eosinophil apoptosis was assessed using flow cytometry. RESULTS: The addition of anti-CD30 mAb significantly increased eosinophil apoptosis compared with controls. In western blot analysis, the addition of anti-CD30 mAb significantly decreased the expression of Bcl-2 and procaspase-9 and -3 and increased the expression of caspase-9 and -3. The addition of caspase-9 or -3 inhibitors decreased anti-CD30 mAb-induced human eosinophil apoptosis. Procaspase-8 or caspase-8 expression was not changed in response to various stimuli. CONCLUSION: Anti-CD30 mAb-induced human eosinophil apoptosis is likely to be mediated through Bcl-2 and caspase-9 and -3.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
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김규언(Kim, Kyu Earn)
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