TY - JOUR
T1 - Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice
AU - Iki, Misako
AU - Tanaka, Kensei
AU - Deki, Hayato
AU - Fujimaki, Mio
AU - Sato, Shingo
AU - Yoshikawa, Soichiro
AU - Yamanishi, Yoshinori
AU - Karasuyama, Hajime
N1 - Funding Information:
The authors thank J. Miyazaki (Osaka University) for providing CAG-Cre mice. This work was supported by research grants from Japan Science and Technology Agency (1A145) (H.K.) and the Japanese Ministry of Education, Culture, Sports, Science and Technology (15H05786 [H.K.] and 15K20969 [Y.Y.]).
Publisher Copyright:
© 2016 by The American Society of Hematology.
PY - 2016/12/22
Y1 - 2016/12/22
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2016-07-729392
DO - 10.1182/blood-2016-07-729392
M3 - Article
C2 - 27789480
AN - SCOPUS:85014891812
SN - 0006-4971
VL - 128
SP - 2909
EP - 2918
JO - Blood
JF - Blood
IS - 25
ER -