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Publication : The Basophil-specific Protease mMCP-8 Provokes an Inflammatory Response in the Skin with Microvascular Hyperpermeability and Leukocyte Infiltration.

First Author  Tsutsui H Year  2017
Journal  J Biol Chem Volume  292
Issue  3 Pages  1061-1067
PubMed ID  27932459 Mgi Jnum  J:239235
Mgi Id  MGI:5828024 Doi  10.1074/jbc.M116.754648
Citation  Tsutsui H, et al. (2017) The Basophil-specific Protease mMCP-8 Provokes an Inflammatory Response in the Skin with Microvascular Hyperpermeability and Leukocyte Infiltration. J Biol Chem 292(3):1061-1067
abstractText  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 alpha-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.
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