The Journal of Experimental Medicine
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Published online 5 March 2001.
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© The Rockefeller University Press, 0022-1007/2001/3/563/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 5, March 5, 2001 563-572

Original Article

Lyn Is Essential for Fc{gamma} Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction

Takae Yuasaa, Masao Onoa, Takeshi Watanabeb, and Toshiyuki Takaia

a Department of Experimental Immunology and the Core Research for Evolutional Science and Technology (CREST) Program of Japan Science and Technology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
b Department of Molecular Immunology, Medical Institute of Bioregulation, Fukuoka 812-8582, Japan
Dept. of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan.81-22-717-850581-22-717-8501

tostakai{at}idac.tohoku.ac.jp

The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (Fc{varepsilon}RI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (Fc{gamma}RIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (Fc{gamma}RIIB) and Lyn to exclude any involvement of inhibitory signaling by Fc{gamma}RIIB, which otherwise downregulates Fc{gamma}RIII-mediated cellular responses. Fc{gamma}RIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow–derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor {alpha} release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, Fc{gamma}RIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.

Key Words: Lyn • Fc receptor • hypersensitivity • mast cells • Arthus reaction

Abbreviations used in this paper: BMMC, bone marrow–derived mast cell; ITAM, immunoreceptor tyrosine–based activation motif; MPO, myeloperoxidase; PMC, peritoneal resident mast cell; TNP, trinitrophenyl.

© 2001 The Rockefeller University Press


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