2007 Fiscal Year Final Research Report Summary
Establishment of a new diagnostic method to identify malignant hyperthermia-susceptible indivicbials by using dendritic cells.
| Project/Area Number |
18591719
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Saitama Medical University |
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Principal Investigator |
KIKUCHI Hirosato Saitama Medical University, Faculty of Medicine, Professor (40034029)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Yasushi Saitama Medical University, Faculty of Medicine, Assistant professor (40364781)
LIU Tian-Yi Saitama Medical University, Faculty of Medicine, Instructor (20406490)
MATSUSHITA Sho Saitama Medical University, Faculty of Medicine, Professor (50167649)
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| Project Period (FY) |
2006 – 2007
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| Keywords | malignant hyperthermia / dendritic cells / ryanodine receptor |
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| Research Abstract |
Malignant hyperthermia (MH) is a disorder of calcium homeostasis in skeletal muscle triggered by anesthetics or succinylcholine that results from mutations in type 1 ryanodine receptor (RyR1). Multiple sites of mutations on RyR1 gene have been made their structure-based diagnosis difficult. Currently, the definitive diagnosis of MH-susceptible individuals requires the use of biopsied muscle. Because of the invasive nature of this test, the establishment of a more efficient and a less invasive diagnostic method has great significance in uncovering the etiology of MH and in the development of preventative and therapeutic strategies. Thereby the identification of other cell types that preferentially express RyR1 expands the possibility for a new diagnostic method. There are three RyR isoforms, and we identified, for the first time that human dendritic cells (DCs) preferentially express RyR1 mRNA among them. The RyR activator, 4-chloro-m-cresol (4CmC), induced Ca^2+ release in DCs, and this response was eliminated by dantrolene, an inhibitor of the RyR1, and was unaffected by xestospongin C, a selective inhibitor of IP3 receptor. Activation of RyR1 reduced LPS-induced IL-10 production, promoted the expression of HLA-DR and CD86, and thereby exhibited an improved capacity to stimulate allogeneic T cells. These findings demonstrate that RyR1-mediated calcium signaling modify diverse DC responses and suggest the feasibility of using DC preparations for the diagnosis of MH.
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