title: The Basophil-specific Protease mMCP-8 Provokes an Inflammatory Response in the Skin with Microvascular Hyperpermeability and Leukocyte Infiltration.
abstract: Basophils have often been erroneously considered to be minor relatives or blood-circulating precursors of tissue-resident mast cells because of some phenotypic similarity between them, including basophilic secretory granules in the cytoplasm. However, recent studies revealed that the repertoire of serine proteases stored in secretory granules is distinct in them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells despite its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker, but its functional property remains uncertain. Here we prepared recombinant mMCP-8 and examined its activity in vitro and in vivo Purified recombinant mMCP-8 showed heat-sensitive proteolytic activity when α-tubulin was used as a substrate. One intradermal shot of mMCP-8, not heat-inactivated, induced cutaneous swelling with increased microvascular permeability in a cyclooxygenase-dependent manner. Moreover, repeated intradermal injection of mMCP-8 promoted skin infiltration of leukocytes, predominantly neutrophils and, to a lesser extent, monocytes and eosinophils, in conjunction with up-regulation of chemokine expression in the skin lesion. These results suggest that mMCP-8 is an important effector molecule in basophil-elicited inflammation, providing novel insights into how basophils exert a crucial and non-redundant role, distinct from that played by mast cells, in immune responses.
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan yamanishi.mbch@tmd.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamanishi
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ohtsuka
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sato
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: From the Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8519, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008407:Mast Cells / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D053802:Tryptases / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D014404:Tubulin; C512639:Mcpt8 protein, mouse; D053802:Tryptases
keywords: basophil; cell migration; chemokine; inflammation; leukocyte; microvascular permeability; serine protease