title: Basophil-derived mouse mast cell protease 11 induces microvascular leakage and tissue edema in a mast cell-independent manner.
abstract: Mouse mast cell protease 11 (mMCP-11) is the most recently identified member of the mouse mast cell tryptase family. This tryptase is preferentially produced by basophils in contrast to other members that are expressed by mast cells but not basophils. Although blood-circulating basophils have long been considered as minor and redundant relatives of tissue-resident mast cells, recent studies illustrated that basophils and mast cells play distinct roles in vivo. To explore the in vivo role of basophil-derived mMCP-11, here we prepared recombinant mMCP-11 and its protease-dead mutant. Subcutaneous injection of the wild-type mMCP-11 but not the mutant induced edematous skin swelling with increased microvascular permeability in a dose-dependent manner. No apparent infiltration of proinflammatory cells including neutrophils and eosinophils was detected in the skin lesions. The cutaneous swelling was abolished by the pretreatment of mice with indomethacin, a cyclooxygenase inhibitor, suggesting the major contribution of prostaglandins to the microvascular leakage. Of note, the cutaneous swelling was elicited even in mast cell-deficient mice, indicating that mast cells are dispensable for the mMCP-11-induced cutaneous swelling. Thus, basophil-derived mMCP-11 can induce microvascular leakage via prostaglandins in a mast cell-independent manner, and may contribute to the development of basophil-mediated inflammatory responses.
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamagishi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ugajin
authors.forename: Shingo
authors.initials: S
authors.lastname: Sato
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D000818:Animals; D001491:Basophils / Q000201:enzymology*; D002199:Capillary Permeability; D004487:Edema / Q000201:enzymology*; D006633:Histamine Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011968:Receptors, Histamine / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053802:Tryptases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D011994:Recombinant Proteins; D053802:Tryptases; C569504:mast cell protease 11, mouse; D007213:Indomethacin