PMID- 11815739
OWN - NLM
STAT- MEDLINE
DCOM- 20020308
LR  - 20180213
IS  - 1018-2438 (Print)
IS  - 1018-2438 (Linking)
VI  - 126
IP  - 4
DP  - 2001 Dec
TI  - TU-572, a potent and selective CD45 inhibitor, suppresses IgE-mediated 
      anaphylaxis and murine contact hypersensitivity reactions.
PG  - 318-24
AB  - BACKGROUND: CD45, receptor-type protein tyrosine phosphatases (PTPases) are 
      essential components of signaling through both the T cell receptor and the B cell 
      antigen receptor. However, the functional significance of CD45 in the signaling 
      pathway through the high-affinity immunoglobulin (Ig) E receptor has not yet been 
      established. In this study, we demonstrate that the potent CD45 inhibitor 
      negatively regulates IgE-dependent anaphylaxis and contact hypersensitivity 
      reactions. METHOD: We have previously found that TU-572, 
      2-[(4-methylthiopyridin-2-yl)methylsulfinyl]-5-isopropoxybenzimidazole, had a 
      potent and selective inhibitory effect against PTPase activity of CD45. Using a 
      CD45 inhibitor, we examined in vitro and in vivo IgE-mediated responses. RESULTS: 
      TU-572 potently inhibited histamine release from rat peritoneal mast cells and 
      mouse systemic anaphylaxis reaction using monoclonal anti-dinitrophenyl (DNP) IgE 
      and DNP-BSA. TU-572 also suppressed the immediate-type hypersensitivity response 
      induced by repeated epicutaneous application of trinitrochlorobenzene in BALB/c 
      mice. CONCLUSION: These findings revealed that the PTPase activity of CD45 played 
      a critical role in signal transduction of IgE-mediated anaphylaxis in vitro and 
      in vivo. PTPase inhibitors such as TU-572 are useful in the treatment of allergic 
      diseases.
CI  - Copyright 2002 S. Karger AG, Basel
FAU - Hamaguchi, T
AU  - Hamaguchi T
AD  - Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, 
      Saitama, Japan. tak.hamaguchi@po.rd.taisho.co.jp
FAU - Takahashi, A
AU  - Takahashi A
FAU - Manaka, A
AU  - Manaka A
FAU - Sato, M
AU  - Sato M
FAU - Osada, H
AU  - Osada H
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Int Arch Allergy Immunol
JT  - International archives of allergy and immunology
JID - 9211652
RN  - 0 (2-((4-methylthiopyridin-2-yl)methylsulfinyl)benzimidazole)
RN  - 0 (Benzimidazoles)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Sulfoxides)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - Z4ZG7O5SZ9 (Picryl Chloride)
SB  - IM
MH  - Anaphylaxis/*drug therapy
MH  - Animals
MH  - Benzimidazoles/*pharmacology/therapeutic use
MH  - Dermatitis, Contact/*drug therapy
MH  - Enzyme Inhibitors/*pharmacology/therapeutic use
MH  - Female
MH  - Histamine Release
MH  - Hypersensitivity, Immediate/drug therapy
MH  - Leukocyte Common Antigens/*drug effects
MH  - Mast Cells/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Picryl Chloride/adverse effects
MH  - Protein Tyrosine Phosphatases/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sulfoxides/*pharmacology/therapeutic use
EDAT- 2002/01/30 10:00
MHDA- 2002/03/09 10:01
CRDT- 2002/01/30 10:00
PHST- 2002/01/30 10:00 [pubmed]
PHST- 2002/03/09 10:01 [medline]
PHST- 2002/01/30 10:00 [entrez]
AID - iaa26318 [pii]
AID - 10.1159/000049529 [doi]
PST - ppublish
SO  - Int Arch Allergy Immunol. 2001 Dec;126(4):318-24. doi: 10.1159/000049529.