Sensitized mast cells migrate toward the antigen: a response regulated by p38 mitogen-activated protein kinase and Rho-associated coiled-coil-forming protein kinase.
Although mast cells accumulate within the mucosal epithelial layer of patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether mast cells sensitized with Ag-specific IgE migrate toward the Ag. MC/9 mast cells sensitized with anti-DNP IgE migrated toward DNP-conjugated human serum albumin. This migration was directional, and the degree was stronger than that induced by stem cell factor. IL-3 and stem cell factor-dependent cultured mast cells derived from mouse bone marrow also migrated toward the Ag. Subsequent migration mediated by the Fc(epsilon)RI was significantly inhibited by incubating the cells with Y-27632, a Rho-associated coiled-coil-forming protein kinase inhibitor, or with SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Both p38 MAPK and MAPK-activated protein kinase (MAPKAPK)2 were activated following Fc(epsilon)RI aggregation, and activation of MAPKAPK2 was almost completely inhibited by 10 microM SB203580. Wortmannin or a low concentration of SB203580 partially inhibited MAPKAPK2, but did not block mast cell migration. In contrast, Y-27632 did not affect the activation of MAPKAPK2. These results indicate that Ag works not only as a stimulant for allergic mediators from IgE-sensitized mast cells, but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of Rho-associated coiled-coil-forming protein kinase may be required for Fc(epsilon)RI-mediated cell migration.
Ishizuka
T
T
First Department of Internal Medicine, Gunma University School of Medicine, Faculty of Health Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan. tamotsui@showa.gunma-u.ac.jp
Okajima
F
F
Ishiwara
M
M
Iizuka
K
K
Ichimonji
I
I
Kawata
T
T
Tsukagoshi
H
H
Dobashi
K
K
Nakazawa
T
T
Mori
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells; D004140:Dinitrophenols / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D007093:Imidazoles / Q000494:pharmacology; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D048369:MAP Kinase Kinase 1; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000502:physiology; D012709:Serum Albumin / Q000276:immunology; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases; D054460:rho-Associated Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D000730:Androstadienes; D004140:Dinitrophenols; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006241:Haptens; D007093:Imidazoles; D007073:Immunoglobulin E; D047908:Intracellular Signaling Peptides and Proteins; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019009:Proto-Oncogene Proteins c-kit; D011725:Pyridines; D017455:Receptors, IgE; D012709:Serum Albumin; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases; D054460:rho-Associated Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C058064:dinitrophenyl-human serum albumin conjugate; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one