Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice

Misako Iki, Kensei Tanaka, Hayato Deki, Mio Fujimaki, Shingo Sato, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2909-2918
Number of pages10
JournalBlood
Volume128
Issue number25
DOIs
Publication statusPublished - Dec 22 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Iki, M., Tanaka, K., Deki, H., Fujimaki, M., Sato, S., Yoshikawa, S., Yamanishi, Y., & Karasuyama, H. (2016). Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice. Blood, 128(25), 2909-2918. https://doi.org/10.1182/blood-2016-07-729392