PMID- 11984598
OWN - NLM
STAT- MEDLINE
DCOM- 20020528
LR  - 20181113
IS  - 1078-8956 (Print)
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 8
IP  - 5
DP  - 2002 May
TI  - A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein 
      inhibits Fc epsilon RI-mediated degranulation.
PG  - 518-21
AB  - Human mast cells and basophils that express the high-affinity immunoglobulin E 
      (IgE) receptor, Fc epsilon receptor 1 (Fc epsilon RI), have key roles in allergic 
      diseases. Fc epsilon RI cross-linking stimulates the release of allergic 
      mediators. Mast cells and basophils co-express Fc gamma RIIb, a low affinity 
      receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose 
      co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity. 
      Here we designed, expressed and tested the human basophil and mast-cell 
      inhibitory function of a novel chimeric fusion protein, whose structure is gamma 
      Hinge-CH gamma 2-CH gamma 3-15aa linker-CH epsilon 2-CH epsilon 3-CH epsilon 4. 
      This Fc gamma Fc epsilon fusion protein was expressed as the predicted 140-kappa 
      D dimer that reacted with anti-human epsilon- and gamma-chain specific 
      antibodies. Fc gamma Fc epsilon bound to both human Fc epsilon RI and Fc gamma 
      RII. It also showed dose- and time-dependent inhibition of antigen-driven 
      IgE-mediated histamine release from fresh human basophils sensitized with IgE 
      directed against NIP (4-hydroxy-3-iodo-5-nitrophenylacetyl). This was associated 
      with altered Syk signaling. The fusion protein also showed increased inhibition 
      of human anti-NP (4-hydroxy-3-nitrophenylacetyl) and anti-dansyl IgE-mediated 
      passive cutaneous anaphylaxis in transgenic mice expressing human Fc epsilon RI 
      alpha. Our results show that this chimeric protein is able to form complexes with 
      both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell and basophil function. 
      This approach, using a Fc gamma Fc epsilon fusion protein to co-aggregate Fc 
      epsilon RI with a receptor containing an immunoreceptor tyrosine-based inhibition 
      motif, has therapeutic potential in IgE- and Fc epsilon RI-mediated diseases.
FAU - Zhu, Daocheng
AU  - Zhu D
AD  - The Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, 
      Department of Medicine, University of California Los Angeles School of Medicine, 
      Los Angeles, California, USA.
FAU - Kepley, Christopher L
AU  - Kepley CL
FAU - Zhang, Min
AU  - Zhang M
FAU - Zhang, Ke
AU  - Zhang K
FAU - Saxon, Andrew
AU  - Saxon A
LA  - eng
GR  - R01 AI015251/AI/NIAID NIH HHS/United States
GR  - R21 AI015251/AI/NIAID NIH HHS/United States
GR  - AI-15251/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Receptors, IgE)
RN  - 0 (Receptors, IgG)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Animals
MH  - Basophil Degranulation Test
MH  - Basophils/*immunology
MH  - Cell Degranulation/immunology
MH  - Humans
MH  - Hypersensitivity/*immunology
MH  - Mast Cells/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Receptors, IgE/genetics/*immunology
MH  - Receptors, IgG/*immunology
MH  - Recombinant Fusion Proteins/*immunology
PMC - PMC1866216
MID - NIHMS2562
EDAT- 2002/05/02 10:00
MHDA- 2002/05/29 10:01
PMCR- 2007/05/08
CRDT- 2002/05/02 10:00
PHST- 2002/05/02 10:00 [pubmed]
PHST- 2002/05/29 10:01 [medline]
PHST- 2002/05/02 10:00 [entrez]
PHST- 2007/05/08 00:00 [pmc-release]
AID - nm0502-518 [pii]
AID - 10.1038/nm0502-518 [doi]
PST - ppublish
SO  - Nat Med. 2002 May;8(5):518-21. doi: 10.1038/nm0502-518.