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Biomedical subjects

Kayoko Sato

Publications and source records attributed to Kayoko Sato.

12 recordsLinked to original sources
PubMed2006

Functional profile of activated dendritic cells in unstable atherosclerotic plaque.

BACKGROUND: Unstable atherosclerotic plaque typically contains an infiltrate of activated macrophages and activated T cells. This study established a functional profile of plaque-residing dendritic cells (DC) to examine whether they can function as Ag-presenting cells to facilitate in situ T-cell activation. METHODS: Carotid artery plaque tissues were collected from 19 asymptomatic and 38 symptomatic patients undergoing endarterectomy. Matched samples of normal coronary artery wall, stable nonruptured plaque, and eroded unstable plaque were harvested from patients with fatal myocardial infarction. Quantitative PCR and immunohistochemistry were used to analyze the tissues for markers of DC activation (CD83, CD86, CCL19,CCL21) and correlate them with T-cell activation (IFN-gamma,TNF-alpha). RESULTS: Carotid artery plaques from patients with ischemic symptoms compared to asymptomatic patients were characterized by the presence of high amount of T-cells (P<0.01) and tissue production of high levels of the T-cell cytokines IFN-gamma (P=0.001) and TNF-alpha (P=0.006). Plaque tissues from patients with ischemic complications contained elevated levels of CD83 (P<0.001), a marker of DC activation, and the DC chemokines CCL19 (P=0.001) and CCL21 (P<0.02). Unstable coronary artery plaques were similarly correlated compared to carotid plaques from symptomatic patients with the accumulation of T cells (P=0.001) and the production of T cell chemokines IFN-gamma (P=0.001) and TNF-alpha (P=0.002). Immunohistochemistry confirmed the presence of CD83(+) DC in the shoulder region of unstable plaques, where they produced the T cell-attracting chemokines CCL19 and CCL21. Mapping of activated DC demonstrated close contact between mature DC and T cells expressing the activation marker CD40 ligand (CD40L). CONCLUSION: Activated and fully mature DC are represented in the inflammatory infiltrate characteristic for unstable carotid and coronary atheroma. Such DC produce chemokines, and thus can regulate the cell traffic into the lesion. Through the expression of the costimulatory ligand CD86, plaque-residing DC can augment T-cell stimulation and provide optimal stimulation conditions for T lymphocytes, resembling the microenvironment in organized lymphoid tissues.

Atherosclerosis↗
PubMed2006

Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha.

BACKGROUND: Unstable atherosclerotic plaque is characterized by an infiltrate of inflammatory cells. Both macrophages and T cells have been implicated in mediating the tissue injury leading to plaque rupture; however, signals regulating their activation remain unidentified. Infectious episodes have been suspected to render plaques vulnerable to rupture. We therefore explored whether plasmacytoid dendritic cells (pDCs) that specialize in sensing bacterial and viral products can regulate effector functions of plaque-residing T cells and thus connect host infection and plaque instability. METHODS AND RESULTS: pDCs were identified in 53% of carotid atheromas (n=30) in which they localized to the shoulder region and produced the potent immunoregulatory cytokine interferon (INF)-alpha. IFN-alpha transcript concentrations in atheroma tissues correlated strongly with plaque instability (P<0.0001). Plaque-residing pDCs responded to pathogen-derived motifs, CpG-containing oligodeoxynucleotides binding to toll-like receptor 9, with enhanced IFN-alpha transcription (P=0.03) and secretion (P=0.007). IFN-alpha emerged as a potent regulator of T-cell function, even in the absence of antigen recognition. Specifically, IFN-alpha induced a 10-fold increase of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface of CD4 T cells (P<0.0001) and enabled them to effectively kill vascular smooth muscle cells (P=0.0003). CONCLUSIONS: pDCs in atherosclerotic plaque sense microbial motifs and amplify cytolytic T-cell functions, thus providing a link between host-infectious episodes and acute immune-mediated complications of atherosclerosis.

Aged↗
PubMed2006

T cell recognition and killing of vascular smooth muscle cells in acute coronary syndrome.

Loss of vascular smooth muscle cells (VSMCs) has been proposed to destabilize the atherosclerotic plaque and contribute to plaque rupture, superimposed thrombosis, and acute coronary syndromes (ACSs). We examined whether VSMCs are susceptible to T cell-induced apoptosis and found that CD4 T cells are highly effective in establishing cell-cell contact with VSMCs and triggering apoptotic death. Visualization of the T cell-VSMC contact zone on the single-cell level revealed that both patient-derived and control CD4 T cells reorganized their cell membrane to assemble an immunologic synapse with the VSMCs. Within 4 to 10 minutes, the membrane proximal signaling molecule ZAP-70 was recruited and phosphorylated. However, only patient-derived CD4 T cells sustained an intact immunologic synapse beyond 10 minutes and generated intracellular calcium signals. CD4 T cells that maintained a synaptic contact and appeared to be responsible for VSMC apoptosis accounted for approximately 20% of the circulating memory T cell population in ACS patients and were rare in the blood of age-matched controls. CD4 T cells from ACS patients were also hyperresponsive to T cell receptor-mediated stimulation when triggered by a superantigen and non-VSMC target cells. Lowered setting of the T cell activation threshold, attributable to excessive amplification of proximal CD3-mediated signals, may contribute to CD4 T cell-mediated killing of VSMCs and promote plaque instability.

Acute Disease↗
PubMed2006

TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque.

Acute coronary syndromes (ACS) are precipitated by a rupture of the atherosclerotic plaque, often at the site of T cell and macrophage infiltration. Here, we show that plaque-infiltrating CD4 T cells effectively kill vascular smooth muscle cells (VSMC). VSMCs sensitive to T cell-mediated killing express the death receptor DR5 (TNF-related apoptosis-inducing ligand [TRAIL] receptor 2), and anti-TRAIL and anti-DR5 antibodies block T cell-mediated apoptosis. CD4 T cells that express TRAIL upon stimulation are expanded in patients with ACS and more effectively induce VSMC apoptosis. Adoptive transfer of plaque-derived CD4 T cells into immunodeficient mice that are engrafted with human atherosclerotic plaque results in apoptosis of VSMCs, which was prevented by coadministration of anti-TRAIL antibody. These data identify that the death pathway is triggered by TRAIL-producing CD4 T cells as a direct mechanism of VSMC apoptosis, a process which may lead to plaque destabilization.

Adoptive Transfer↗
PubMed2005

Dual-subtype vaccine (Fel-O-Vax FIV) protects cats against contact challenge with heterologous subtype B FIV infected cats.

Fel-O-Vax FIV is a dual-subtype vaccine consisting of inactivated whole viruses of subtype A (Petaluma strain) and subtype D (Shizuoka strain). The efficacy of this vaccine against heterologous subtype A strain challenge was demonstrated, but it is unclear whether the result reflects efficacy in the field. In this study, we evaluated the efficacy of this vaccine against contact challenge by exposing both vaccinated and unvaccinated control animals with cats infected with Aomori-2 strain belonging to subtype B, a subtype prevalent in many regions of the world. Nineteen specific-pathogen-free (SPF) cats were divided into a vaccinated group (six cats), an unvaccinated control group (eight cats), and a challenge group (five cats), and maintained in the same room. Cats were monitored for FIV proviral DNA by nested PCR and for FIV-specific antibody levels by ELISA. After 1 year of commingling, each cat in the vaccinated group was given a booster dose. In addition, the original challenge group was removed and replaced with another challenge group of SPF cats, which were inoculated with the Aomori-2 strain. FIV infection was confirmed in four of the eight animals in the unvaccinated control group by the 29th week in the second year of commingling. In contrast, all of the animals were negative in the vaccinated group. These findings confirmed the efficacy of this vaccine against heterologous stains classified as subtype B, and suggested that the vaccine exhibits broad efficacy against genetically diverse FIV.

Animals↗
PubMed2005

Redistributions of macrophages expressing the macrophage galactose-type C-type lectin (MGL) during antigen-induced chronic granulation tissue formation.

Cell surface lectins are known to regulate trafficking of cells in the immune system, yet the role of macrophage galactose-type C-type lectin 1 and 2 (MGL1/2) is poorly understood. In this study, antigen-specific chronic inflammation was induced in a subcutaneous air pouch model in mice, and distribution of cells expressing MGL1/2 was investigated. Azobenzenearsonate-conjugated acetylated BSA, used as an antigen, was introduced into an air pouch of immunized mice, and tissue formation and distribution of MGL1/2-positive cells in the sub-dermal regions was examined. Thickness of the inflammatory tissue and number of MGL1/2-positive cells simultaneously reached the maximum at day 4 and returned to the control level at day 6 or 8. When additional antigenic challenges were given, a chronic granulation tissue, which had two distinct layers, was generated. In the chronic tissue, CD11b-positive/MGL1/2-negative cells were abundant in the area close to the antigenic stimulus, while the area far from the antigenic stimulus was dominated by MGL1/2-positive/CD11b-negative or -low cells. Flow cytometric analyses of isolated cells from the granulation tissue revealed that MGL1/2-positive cells expressed MHC class II at high levels, CD11b at low levels but no CD11c. MGL1/2-positive and -negative fractions were separated from cells in the granulation tissue and a higher level of IL-1alpha messenger RNA than negative populations was detected in the MGL1/2-positive fraction by the semi-quantitative reverse transcription-PCR method. IL-1alpha production by MGL1/2-positive cells was also immunohistochemically detected. Results suggest that MGL1/2-positive cells represent a distinct sub-population of macrophages, having unique functions in the generation and maintenance of granulation tissue induced by antigenic stimuli.

Animals↗
PubMed2005

Lack of antigen-specific tissue remodeling in mice deficient in the macrophage galactose-type calcium-type lectin 1/CD301a.

Macrophage galactose-type C-type lectins (MGLs), which were recently named CD301, have 2 homologues in mice: MGL1 and MGL2. MGLs are expressed on macrophages and immature dendritic cells. The persistent presence of granulation tissue induced by a protein antigen was observed in wild-type mice but not in mice lacking an endogenous, macrophage-specific, galactose-type calcium-type lectin 1 (MGL1) in an air pouch model. The anti-MGL1 antibody suppressed the granulation tissue formation in wild-type mice. A large number of cells, present only in the pouch of MGL1-deficient mice, were not myeloid or lymphoid lineage cells and the number significantly declined after administration of interleukin 1 alpha (IL-1alpha) into the pouch of MGL1-deficient mice. Furthermore, granulation tissue was restored by this treatment and the cells obtained from the pouch of MGL1-deficient mice were incorporated into the granulation tissue when injected with IL-1alpha. Taken together, MGL1 expressed on a specific subpopulation of macrophages that secrete IL-1alpha was proposed to regulate specific cellular interactions crucial to granulation tissue formation.

Air↗
PubMed2005

Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1.

The role of a macrophage galactose-type calcium-type lectin-1 (MGL1) in antigen-independent granulation tissue formation was investigated. Granulation tissue was induced by injection of carrageenan in an air pouch and distribution of macrophages expressing MGL1/2 was histologically examined. MGL1/2-positive cells were not observed in the granulation tissue induced by carrageenan though these cells were present in dermis. This was distinct from the fact that MGL1/2-positive cells were abundant in granulation tissue induced by antigenic stimulation. CD11b-positive cells were in dermis and carrageenan-induced granulation tissue. Because antigen-induced granulation tissue formation was previously shown to decrease in MGL1-deficient mice or after treatment with anti-MGL1 antibody, we investigated the effects of MGL1-deficient status on carrageenan-induced granulation tissue formation. The thickness of granulation tissue was almost identical between wild-type and MGL1-deficient mice. It is highly likely that MGL1-positive cells are not involved in tissue remodeling when inflammation is driven by nonspecific stimuli.

Animals↗
PubMed2005

[Complex decongestive physiotherapy (CDP)].

Complex decongestive physiotherapy (CDP) is a representative conservative treatment for lymph edema symptoms conducted by combination of various physical therapies. In the mid-twentieth century, Dr. Michael Foeldi structured CDP. Regular treatments by CDP will relieve lymph edema symptoms as well as mental and physical distress, leading to enhancement of ADL and QOL. In Europe, CDP is served by close tie-up of physiotherapists and massotherapists under supervision of medical doctors. For effective CDP, early start of the treatment and full guidance of life style are recommended.

Humans↗
PubMed2004

HZE radiation effects for hereditary renal carcinomas.

Eker rat known as a model of hereditary renal carcinoma (RC) is an example of Mendelian dominantly inherited predisposition to a specific cancer in experimental animals. We investigate the effects of simulated space radiation on carcinogenesis using HIMAC. We estimated RBE from the Eker rats exposed to the heavy-ions, C (290 MeV/u) and Fe (500 MeV/u) ions, comparing to the effects of X-ray irradiation. Pregnant rats were exposed to C and Fe ions and X-rays with a single dose of 1 Gy, 2 Gy, 3 Gy on day 19 of gestation. The offspring were sacrificed at 8 weeks of age. We evaluated organ weights and tumor genesis. The weights of thymus, lung, liver, spleen were found to be no difference from the control at 1 Gy irradiation but 50% decrease at 3 Gy irradiation. We found in the irradiated animal that kidney, brain and testis were very sensitive organs of which the weight decreased to approximately 80% at 1 Gy and to 40% at 3 Gy irradiations. Based on the dose-response relationship of the radiation-induced carcinoma, averaged RBE ware calculated to be 1.1 for C-ion, 1.6 for Fe-ion.

Animals↗