Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria
Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a recep...
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| Published in | Journal of allergy and clinical immunology Vol. 134; no. 3; pp. 622 - 633.e9 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
Elsevier Inc
01.09.2014
Elsevier Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.
We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs.
MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca2+ influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays.
The number of MrgX2+ skin MCs and the percentage of MrgX2+ MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2.
MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. |
|---|---|
| AbstractList | Background Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy. Objective We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs. Methods MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca2+influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2levels were measured by using enzyme immunoassays. Results The number of MrgX2+skin MCs and the percentage of MrgX2+MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2. Conclusion MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.BACKGROUNDWheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy.We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs.OBJECTIVEWe sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs.MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca(2+) influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays.METHODSMrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca(2+) influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays.The number of MrgX2(+) skin MCs and the percentage of MrgX2(+) MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2.RESULTSThe number of MrgX2(+) skin MCs and the percentage of MrgX2(+) MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2.MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU.CONCLUSIONMrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. Background Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy. Objective We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs. Methods MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca2+ influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays. Results The number of MrgX2+ skin MCs and the percentage of MrgX2+ MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2. Conclusion MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy. We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs. MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca(2+) influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays. The number of MrgX2(+) skin MCs and the percentage of MrgX2(+) MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2. MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. Wheal reactions to intradermally injected neuropeptides, such as substance P (SP) and vasoactive intestinal peptide, are significantly larger and longer lasting in patients with chronic urticaria (CU) than in nonatopic control (NC) subjects. Mas-related gene X2 (MrgX2) has been identified as a receptor for basic neuropeptides, such as SP and vasoactive intestinal peptide. Mast cell (MC) responsiveness to eosinophil mediators contributes to the late-phase reaction of allergy. We sought to compare the frequency of MrgX2 expression in skin MCs from patients with CU and NC subjects and to identify the receptor for basic eosinophil granule proteins on human skin MCs. MrgX2 expression was investigated by using immunofluorescence in skin tissues from NC subjects and patients with severe CU and on skin-derived cultured MCs. MrgX2 expression in human MCs was reduced by using a lentiviral small hairpin RNA silencing technique. Ca2+ influx was measured in CHO cells transfected with MrgX2 in response to eosinophil granule proteins. Histamine and prostaglandin D2 levels were measured by using enzyme immunoassays. The number of MrgX2+ skin MCs and the percentage of MrgX2+ MCs in all MCs in patients with CU were significantly greater than those in NC subjects. Eosinophil infiltration in urticarial lesions was observed in 7 of 9 patients with CU. SP, major basic protein, and eosinophil peroxidase, but not eosinophil-derived neurotoxin, induced histamine release from human skin MCs through MrgX2. MrgX2 might be a new target molecule for the treatment of wheal reactions in patients with severe CU. |
| Author | Hayama, Koremasa Terui, Tadashi Fujitani, Yasushi Nunomura, Satoshi Kuroda, Kazumichi Kashiwakura, Jun-ichi Ra, Chisei Sasaki-Sakamoto, Tomomi Okayama, Yoshimichi Kita, Hirohito Kikukawa, Yusuke Fujisawa, Daisuke |
| Author_xml | – sequence: 1 givenname: Daisuke surname: Fujisawa fullname: Fujisawa, Daisuke organization: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan – sequence: 2 givenname: Jun-ichi orcidid: 0000-0001-7124-2275 surname: Kashiwakura fullname: Kashiwakura, Jun-ichi organization: Laboratory for Allergic Disease, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan – sequence: 3 givenname: Hirohito surname: Kita fullname: Kita, Hirohito organization: Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minn – sequence: 4 givenname: Yusuke orcidid: 0000-0002-5603-3181 surname: Kikukawa fullname: Kikukawa, Yusuke organization: Pharmaceutical Research Division, Takeda Pharmaceutical Company, Fujisawa, Japan – sequence: 5 givenname: Yasushi surname: Fujitani fullname: Fujitani, Yasushi organization: Pharmaceutical Research Division, Takeda Pharmaceutical Company, Fujisawa, Japan – sequence: 6 givenname: Tomomi surname: Sasaki-Sakamoto fullname: Sasaki-Sakamoto, Tomomi organization: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan – sequence: 7 givenname: Kazumichi surname: Kuroda fullname: Kuroda, Kazumichi organization: Department of Microbiology, Nihon University School of Medicine, Tokyo, Japan – sequence: 8 givenname: Satoshi surname: Nunomura fullname: Nunomura, Satoshi organization: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan – sequence: 9 givenname: Koremasa surname: Hayama fullname: Hayama, Koremasa organization: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan – sequence: 10 givenname: Tadashi orcidid: 0000-0002-0275-4311 surname: Terui fullname: Terui, Tadashi organization: Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan – sequence: 11 givenname: Chisei surname: Ra fullname: Ra, Chisei organization: Department of Microbiology, Nihon University School of Medicine, Tokyo, Japan – sequence: 12 givenname: Yoshimichi surname: Okayama fullname: Okayama, Yoshimichi email: okayama.yoshimichi@nihon-u.ac.jp organization: Allergy and Immunology Group, Research Institute of Medical Science, Nihon University School of Medicine, Tokyo, Japan |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28828574$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/24954276$$D View this record in MEDLINE/PubMed |
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| Title | Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria |
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