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Published on: May 27, 2015
Basophil-derived mouse mast cell protease 11 induces microvascular leakage and tissue edema in a mast
Hirofumi Yamagishi1, Yasuhiro Mochizuki, Takao Hamakubo
1Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
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.
Insights
Basophil-derived mouse mast cell protease 11 (mMCP-11) induces skin swelling and microvascular leakage. This occurs independently of mast cells, highlighting basophils
Area of Science:
- Immunology
- Biochemistry
Background:
- Mouse mast cell protease 11 (mMCP-11) is a tryptase predominantly produced by basophils, unlike other family members expressed by mast cells.
- Basophils and mast cells exhibit distinct in vivo roles, challenging the traditional view of basophils as minor cell types.
Purpose of the Study:
- To investigate the in vivo function of basophil-derived mMCP-11.
- To elucidate the mechanisms underlying mMCP-11-induced inflammatory responses.
Main Methods:
- Preparation of recombinant wild-type mMCP-11 and a protease-dead mutant.
- Subcutaneous injection of mMCP-11 into mice to assess skin reactions.
- Evaluation of microvascular permeability, cell infiltration, and the effect of cyclooxygenase inhibition.
- Experiments were conducted in both wild-type and mast cell-deficient mice.
Main Results:
- Wild-type mMCP-11 induced dose-dependent edematous skin swelling and increased microvascular permeability.
- The protease-dead mutant did not elicit these responses.
- Cutaneous swelling was mediated by prostaglandins, as indicated by abolition with indomethacin.
- Inflammatory cell infiltration, including neutrophils and eosinophils, was not observed.
- mMCP-11-induced swelling occurred in mast cell-deficient mice, confirming mast cell independence.
Conclusions:
- Basophil-derived mMCP-11 directly induces microvascular leakage.
- The mechanism involves prostaglandins and is independent of mast cells.
- mMCP-11 may play a significant role in basophil-mediated inflammatory conditions.
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