The basophil-specific protease mMCP-8 provokes an inflammatory response in the skin with microvascular hyperpermeability and leukocyte infiltration

Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1061-1067
Number of pages7
JournalJournal of Biological Chemistry
Volume292
Issue number3
DOIs
Publication statusPublished - Jan 20 2017
Externally publishedYes

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Basophils
Infiltration
Skin
Leukocytes
Peptide Hydrolases
Mast Cells
Secretory Vesicles
Hot Temperature
Intradermal Injections
Capillary Permeability
Serine Proteases
Tubulin
Prostaglandin-Endoperoxide Synthases
Mouse Mcpt8 protein
Chemokines
Eosinophils
Names
Swelling
Monocytes
Cytoplasm

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The basophil-specific protease mMCP-8 provokes an inflammatory response in the skin with microvascular hyperpermeability and leukocyte infiltration. / Tsutsui, Hidemitsu; Yamanishi, Yoshinori; Ohtsuka, Hiromi; Sato, Shingo; Yoshikawa, Soichiro; Karasuyama, Hajime.

In: Journal of Biological Chemistry, Vol. 292, No. 3, 20.01.2017, p. 1061-1067.

Research output: Contribution to journalArticle

Tsutsui, Hidemitsu ; Yamanishi, Yoshinori ; Ohtsuka, Hiromi ; Sato, Shingo ; Yoshikawa, Soichiro ; Karasuyama, Hajime. / The basophil-specific protease mMCP-8 provokes an inflammatory response in the skin with microvascular hyperpermeability and leukocyte infiltration. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 3. pp. 1061-1067.
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