9 research outputs found
Antiatherosclerotic phenotype of perivascular adipose tissue surrounding the saphenous vein in coronary artery bypass grafting
冠動脈バイパス術(CABG)で大伏在静脈(SV)グラフトの血管周囲脂肪組織(PVAT)を温存したまま使用するNo-touch法が良好な成績を収め注目されている.本研究では術中に各種PVATを採取して組織性状と遺伝子発現を比較検討した.SV-PVATは冠動脈や大動脈のPVATに比してM1マクロファージの浸潤や炎症性サイトカイン発現が低く,No-touch法の成績向上に寄与している可能性が示唆された
Targeted Delivery of Immunomodulators to Lymph Nodes
SUMMARY Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node address in molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo
Damage caused by the 1989 OFF-IZU Peninsula Earthquakes
Damage caused by the earthquake swarm off-shore of the Izu Peninsula, which started on June 30, particularly by the largest earthquake of July 9 of magnitude 5.5, was investigated. In spite of the large ground accelerations (233 gal) recorded on the basement of Ito City Hall, no severe damage to structures was observed, except that the ridge roof tiles of many houses fell off and tombstones in some cemeteries fell over. More than 90 percent of tombstones fell down in Hosenji temple, which stands on reclaimed ground on a hill side. This damage indicates that the vertical ground motion was particularly large, due to the short epicentral distance. Normal functioning of life line systems, i.e., gas, water, electricity, telephone and railways recovered within several hours of the earthquake. Damage was concentrated in the area around the JR (Japan Railways) Ito station and the Usami district about 2 km west of the epicenter. Each areas is no an alluvial basin surrounded by rocky hills. Because of the heavy rain before the earthquake, the ground contained much water and the retaining walls of reclaimed land broke, resulting in uneven settlement of the ground and subsidence of houses. Although there was relatively light damage to structures, unusual rumbling in the ground due to the movement of magma frightened people, and they witnessed the under-sea eruption on July 13. Also, some citizens fled due to rumors of a possible tsunami. Ito, a famous swimming resort in Japan, suffered large economical damage due to the cancellation of hotel reservations
Salt Accelerates Allograft Rejection through Serum- and Glucocorticoid-Regulated Kinase-1–Dependent Inhibition of Regulatory T Cells
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Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ
Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ −/− and PI3Kδ D910A/D910A mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ −/−, but not PI3Κδ D910A/D910A, recipients exhibit indefinite prolongation of heart allograft survival. PI3Kδ D910A/D910A Tregs have increased apoptosis and impaired survival. Selective inhibition of PI3Kγ and PI3Kδ (using PI3Kδ and dual PI3Kγδ chemical inhibitors) shows that PI3Kγ inhibition compensates for the negative effect of PI3Kδ inhibition on long-term allograft survival. These data serve as a basis for future PI3K-based immune therapies for transplantation
Antiatherosclerotic phenotype of perivascular adipose tissue surrounding the saphenous vein in coronary artery bypass grafting
Ischemia augments alloimmune injury through IL-6-driven CD4+ alloreactivity
Abstract Ischemia reperfusion injuries (IRI) are unavoidable in solid organ transplantation. IRI augments alloimmunity but the mechanisms involved are poorly understood. Herein, we examined the effect of IRI on antigen specific alloimmunity. We demonstrate that ischemia promotes alloimmune activation, leading to more severe histological features of rejection, and increased CD4+ and CD8+ T cell graft infiltration, with a predominantly CD8+ IFNγ+ infiltrate. This process is dependent on the presence of alloreactive CD4+ T cells, where depletion prevented infiltration of ischemic grafts by CD8+ IFNγ+ T cells. IL-6 is a known driver of ischemia-induced rejection. Herein, depletion of donor antigen-presenting cells reduced ischemia-induced CD8+ IFNγ+ allograft infiltration, and improved allograft outcomes. Following prolonged ischemia, accelerated rejection was observed despite treatment with CTLA4Ig, indicating that T cell costimulatory blockade failed to overcome the immune activating effect of IRI. However, despite severe ischemic injury, treatment with anti-IL-6 and CTLA4Ig blocked IRI-induced alloimmune injury and markedly improved allograft survival. We describe a novel pathway where IRI activates innate immunity, leading to upregulation of antigen specific alloimmunity, resulting in chronic allograft injury. Based on these findings, we describe a clinically relevant treatment strategy to overcome the deleterious effect of IRI, and provide superior long-term allograft outcomes