title: Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice.
abstract: Recent studies have identified nonredundant roles for basophils in immune responses including allergy and protective immunity. It is well known that activated basophils release granule contents such as histamine and proteases as do mast cells. However, the functional significance of basophil-derived proteases remains poorly understood in contrast to those released from mast cells. For this study we generated a line of knockout (KO) mice deficient for mouse mast cell protease-11 (mMCP-11) that is preferentially expressed by basophils rather than mast cells. In spite of normal development of basophils, the mMCP-11-deficient mice showed amelioration of immunoglobulin E-mediated chronic allergic inflammation (IgE-CAI), with reduction of cutaneous swelling, microvascular permeability, and leukocyte infiltration in the skin lesion, when KO mice were compared with wild-type mice. Repeated administration of recombinant mMCP-11 in the skin induced infiltration of leukocytes, including basophils, in a tryptase activity-dependent manner. The transwell migration assay in vitro suggested that mMCP-11-mediated proteolytic products of serum protein promoted migration of basophils, eosinophils, and macrophages via 1 or more G protein-coupled receptors. Thus, basophil tryptase mMCP-11 is a crucial effector molecule for the induction of IgE-CAI. This is the first demonstration that the basophil-derived protease plays a significant role in vivo.
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Misako
authors: M
authors: Iki
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Kensei
authors: K
authors: Tanaka
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Hayato
authors: H
authors: Deki
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Mio
authors: M
authors: Fujimaki
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Shingo
authors: S
authors: Sato
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Soichiro
authors: S
authors: Yoshikawa
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Yoshinori
authors: 0000-0002-9598-3542
authors: Y
authors: Yamanishi
authors: Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Hajime
authors: H
authors: Karasuyama
mesh_terms: D000818:Animals; D001491:Basophils / Q000201:enzymology*; D002199:Capillary Permeability; D002465:Cell Movement; D002908:Chronic Disease; D006967:Hypersensitivity / Q000150:complications / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation / Q000150:complications / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059748:Proteolysis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012867:Skin / Q000098:blood supply / Q000473:pathology; D053802:Tryptases / Q000172:deficiency / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; D007073:Immunoglobulin E; D053802:Tryptases; C569504:mast cell protease 11, mouse