IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion.
Mast cells are the major effector cells for immediate hypersensitivity and chronic allergic reactions. These cells accumulate in mucosal tissues of allergic reactions, where immunoglobulin E (IgE) is produced locally. Here we provide evidence that, in addition to antigen that can attract IgE-bound mast cells, the type of IgE molecules that efficiently activate mast cells can promote the migration of mast cells in the absence of antigen. IgE- and IgE+Ag-mediated migration involves an autocrine/paracrine secretion of soluble factors including adenosine, leukotriene B4, and several chemokines. Their secretion depends on 2 tyrosine kinases, Lyn and Syk, and they are agonists of G-protein-coupled receptors and signal through phosphatidylinositol 3-kinase gamma, leading to mast cell migration. In mouse experiments, naive mast cells are attracted to IgE, and IgE-sensitized mast cells are attracted to antigen. Therefore, IgE and antigen are implicated in mast cell accumulation at allergic tissue sites with local high IgE levels.
Kitaura
Jiro
J
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10 355 Science Center Dr, San Diego, CA 92121, USA.
Kinoshita
Tatsuya
T
Matsumoto
Masaaki
M
Chung
Shaun
S
Kawakami
Yuko
Y
Leitges
Michael
M
Wu
Dianqing
D
Lowell
Clifford A
CA
Kawakami
Toshiaki
T
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D019898:Autocrine Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology* / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D019899:Paracrine Communication / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism
D000941:Antigens; D018925:Chemokines; D016023:Integrins; D043562:Receptors, G-Protein-Coupled; D017455:Receptors, IgE; D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases