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Ovalbumin fused with diphtheria toxin protects mice from ovalbumin induced anaphylactic shock

Authors
 Bong Ki Lee  ;  Young Gun Yoo  ;  Won Young Lee  ;  Chun Soo Hong  ;  Jae Ku Park  ;  Jai Youl Ro 
Citation
 YONSEI MEDICAL JOURNAL, Vol.42(1) : 91-105, 2001 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2001
MeSH
Anaphylaxis/prevention & control* ; Animals ; B-Lymphocytes/immunology ; Female ; Histamine Release/drug effects ; Immunoglobulin E/metabolism ; Interferon-gamma/biosynthesis ; Interleukin-4/biosynthesis ; Lymphocyte Activation/drug effects ; Mast Cells/metabolism ; Mice ; Mice, Inbred BALB C ; Ovalbumin/immunology* ; Recombinant Fusion Proteins/therapeutic use*
Keywords
Immunotherapy ; fusion protein ; spleen index ; IL-4 ; IFN-γ ; histamine ; IgE
Abstract
For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rates and the risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic in normal mice. The effect of OVA-DT on the biological functions of mast cells was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production of IFN-γ by splenic lymphocytes were found to increase, but the production of IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA-specific Th2 to OVA-specific Thl is suggested.

These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, including mast cells and B cells.
Files in This Item:
T200103719.pdf Download
DOI
10.3349/ymj.2001.42.1.91
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Lee, Bong Ki(이봉기)
Lee, Won Young(이원영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143067
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