The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
J.l. Gaillard - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory effect of αS1- and αS2-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat Aortic Tissue ex vivo, and renovascular hypertensive rats in vivo
Journal of Dairy Science, 2010Co-Authors: D Rousseau-ralliard, F. Goirand, S. Tardivel, A. Lucas, Florence Algaron, Daniel Mollé, Veronique Robert, D. Auchère, J.f. Boudier, J.l. GaillardAbstract:A great number of milk-derived peptides have been shown to exhibit angiotensin converting enzyme (ACE) inhibitory properties and thus potential utility in the regulation of blood pressure. The present work aimed to investigate the effects of 2 milk trypsin hydrolysates from αS1- and αS2-casein (CH1 and CH2, respectively) on ACE activity evaluated in human umbilical vein endothelial cells (HUVEC) in vitro, rat Aortic Tissues ex vivo, and renovascular hypertensive rat in vivo. Incubation of HUVEC and rat Aortic Tissues with CH1 or CH2 induced a concentration-dependent inhibition of hydrolysis of the ACE substrate hippuryl-histidylleucine (HHL), the hydrolysates being much less potent than perindopril (an ACE inhibitor). However, in contrast to perindopril, CH1 and CH2 failed to modify angiotensin I-induced Aortic ring vasoconstriction. The HPLC profiles of rat plasma after intragastric administration were variable among individuals but none of the observed peaks corresponded to peptides comprising CH1 or CH2 or to fragments of these peptides. During 4 wk of cardiovascular monitoring, in hydrolysate-fed renovascular hypertensive rats, systolic blood pressure weakly decreased compared with the control group. However, the CH1-fed hypertensive rats exhibited a decrease of heart rate during the nocturnal period of activity. To conclude, our results show that CH1 and CH2 inhibited ACE activity in HUVEC and rat Aortic Tissue but failed to antagonize the Aortic-constricting effects of the natural agonist angiotensin I. Moreover, we demonstrated that CH1, to a greater extent than CH2, can slightly affect cardiovascular parameters although the ingested bioactive
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Inhibitory effect of αS1- and αS2-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat Aortic Tissue ex vivo, and renovascular hypertensive rats in vivo.
Journal of dairy science, 2010Co-Authors: D Rousseau-ralliard, F. Goirand, S. Tardivel, A. Lucas, Florence Algaron, Daniel Mollé, Veronique Robert, D. Auchère, J.f. Boudier, J.l. GaillardAbstract:Abstract A great number of milk-derived peptides have been shown to exhibit angiotensin converting enzyme (ACE) inhibitory properties and thus potential utility in the regulation of blood pressure. The present work aimed to investigate the effects of 2 milk trypsin hydrolysates from α S1 - and α S2 -casein (CH1 and CH2, respectively) on ACE activity evaluated in human umbilical vein endothelial cells (HUVEC) in vitro, rat Aortic Tissues ex vivo, and renovascular hypertensive rat in vivo. Incubation of HUVEC and rat Aortic Tissues with CH1 or CH2 induced a concentration-dependent inhibition of hydrolysis of the ACE substrate hippuryl-histidyl-leucine (HHL), the hydrolysates being much less potent than perindopril (an ACE inhibitor). However, in contrast to perindopril, CH1 and CH2 failed to modify angiotensin I-induced Aortic ring vasoconstriction. The HPLC profiles of rat plasma after intragastric administration were variable among individuals but none of the observed peaks corresponded to peptides comprising CH1 or CH2 or to fragments of these peptides. During 4 wk of cardiovascular monitoring, in hydrolysate-fed renovascular hypertensive rats, systolic blood pressure weakly decreased compared with the control group. However, the CH1-fed hypertensive rats exhibited a decrease of heart rate during the nocturnal period of activity. To conclude, our results show that CH1 and CH2 inhibited ACE activity in HUVEC and rat Aortic Tissue but failed to antagonize the Aortic-constricting effects of the natural agonist angiotensin I. Moreover, we demonstrated that CH1, to a greater extent than CH2, can slightly affect cardiovascular parameters although the ingested bioactive peptides could not be detected in the blood.
Yoshinori Seko - One of the best experts on this subject based on the ideXlab platform.
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Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in Aortic Tissue with Takayasu's arteritis.
Journal of vascular research, 2004Co-Authors: Yoshinori Seko, Kazuyuki Sugishita, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Ryozo NagaiAbstract:To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in Aortic Tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in Aortic Tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the Aortic Tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the Aortic Tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated Aortic Tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.
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Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in the Aortic Tissue of a patient with atherosclerotic Aortic aneurysm.
International angiology : a journal of the International Union of Angiology, 1998Co-Authors: Yoshinori Seko, Osamu Sato, Hideo Yagita, Ko Okumura, A Takagi, Takahashi N, Yoshio YazakiAbstract:We report a rare case of an atherosclerotic Aortic aneurysm with lymphocyte infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage was restricted. Immunohistochemical studies showed that the infiltrating cells mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and 65-kD heat-shock protein (HSP-65) was not strongly expressed in the Aortic Tissue. Although the immunohistochemical data were consistent with an ordinary atherosclerotic Aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune mechanism was involved in the pathogenesis of this case similar to Takayasu's arteritis, in which massive infiltration of delta T lymphocytes and strong expression of HSP-65 in the Aortic Tissue are characteristic.
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Perforin-secreting killer cell infiltration in the Aortic Tissue of patients with atherosclerotic Aortic aneurysm.
Japanese circulation journal, 1997Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Cell-mediated immunity has been implicated in the pathogenesis of vascular cell injury in patients with atherosclerotic Aortic aneurysms. To clarify the immunologic mechanisms involved, we examined the expression of a cytolytic factor, perforin, in infiltrating cells from Aortic Tissue samples taken from 6 patients with atherosclerotic Aortic aneurysms. Immunohistochemical studies showed that the infiltrating cells consisted mainly of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and T helper cells, and that perforin was expressed in NK cells and CTLs. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly on to the surface of arterial vascular cells. These findings provide the first direct evidence that some of the infiltrating cells in the Aortic Tissue consist of killer cells, and strongly suggest that these killer cells, especially NK cells and CTLs, may play a critical role in the vascular cell injury caused by atherosclerotic Aortic aneurysm by releasing perforin.
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Restricted Usage of T-Cell Receptor Vα-Vβ Genes in Infiltrating Cells in Aortic Tissue of Patients With Takayasu’s Arteritis
Circulation, 1996Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Background Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu’s arteritis. Methods and Results To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu’s arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Vα and Vβ genes in infiltrating cells in the Aortic Tissue of patients with Takayasu’s arteritis and atherosclerotic Aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Vα as well as Vβ gene transcripts in Takayasu’s arteritis were restricted. The infiltrating cells expressing Vα2, Vα16, Vα17, Vβ7, and Vβ13.1 were found in 3 of 4 patients. In contrast, TCR Vα-Vβ repertoires in atherosclerotic Aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gene expression between the two diseases. Conclusions The restricted usage of TCR Vα as well as Vβ genes by infiltrating T cells in Takayasu’s arteritis may indicate that a specific antigen in the Aortic Tissue was targeted. Our findings provide the evidence that distinct immunological mechanisms are involved in the pathogenesis of Takayasu’s arteritis and atherosclerotic Aortic aneurysm.
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perforin secreting killer cell infiltration and expression of a 65 kd heat shock protein in Aortic Tissue of patients with takayasu s arteritis
Journal of Clinical Investigation, 1994Co-Authors: Yoshinori Seko, Hideo Yagita, Ko Okumura, S Minota, Akemi Kawasaki, Yoichi Shinkai, K Maeda, O Sato, A Takagi, Yusuke TadaAbstract:Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of Aortic Tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the Aortic Tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the Aortic Tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the Aortic Tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.
Yoshio Yazaki - One of the best experts on this subject based on the ideXlab platform.
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Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in the Aortic Tissue of a patient with atherosclerotic Aortic aneurysm.
International angiology : a journal of the International Union of Angiology, 1998Co-Authors: Yoshinori Seko, Osamu Sato, Hideo Yagita, Ko Okumura, A Takagi, Takahashi N, Yoshio YazakiAbstract:We report a rare case of an atherosclerotic Aortic aneurysm with lymphocyte infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage was restricted. Immunohistochemical studies showed that the infiltrating cells mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and 65-kD heat-shock protein (HSP-65) was not strongly expressed in the Aortic Tissue. Although the immunohistochemical data were consistent with an ordinary atherosclerotic Aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune mechanism was involved in the pathogenesis of this case similar to Takayasu's arteritis, in which massive infiltration of delta T lymphocytes and strong expression of HSP-65 in the Aortic Tissue are characteristic.
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Perforin-secreting killer cell infiltration in the Aortic Tissue of patients with atherosclerotic Aortic aneurysm.
Japanese circulation journal, 1997Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Cell-mediated immunity has been implicated in the pathogenesis of vascular cell injury in patients with atherosclerotic Aortic aneurysms. To clarify the immunologic mechanisms involved, we examined the expression of a cytolytic factor, perforin, in infiltrating cells from Aortic Tissue samples taken from 6 patients with atherosclerotic Aortic aneurysms. Immunohistochemical studies showed that the infiltrating cells consisted mainly of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and T helper cells, and that perforin was expressed in NK cells and CTLs. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly on to the surface of arterial vascular cells. These findings provide the first direct evidence that some of the infiltrating cells in the Aortic Tissue consist of killer cells, and strongly suggest that these killer cells, especially NK cells and CTLs, may play a critical role in the vascular cell injury caused by atherosclerotic Aortic aneurysm by releasing perforin.
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Restricted Usage of T-Cell Receptor Vα-Vβ Genes in Infiltrating Cells in Aortic Tissue of Patients With Takayasu’s Arteritis
Circulation, 1996Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Background Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu’s arteritis. Methods and Results To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu’s arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Vα and Vβ genes in infiltrating cells in the Aortic Tissue of patients with Takayasu’s arteritis and atherosclerotic Aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Vα as well as Vβ gene transcripts in Takayasu’s arteritis were restricted. The infiltrating cells expressing Vα2, Vα16, Vα17, Vβ7, and Vβ13.1 were found in 3 of 4 patients. In contrast, TCR Vα-Vβ repertoires in atherosclerotic Aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gene expression between the two diseases. Conclusions The restricted usage of TCR Vα as well as Vβ genes by infiltrating T cells in Takayasu’s arteritis may indicate that a specific antigen in the Aortic Tissue was targeted. Our findings provide the evidence that distinct immunological mechanisms are involved in the pathogenesis of Takayasu’s arteritis and atherosclerotic Aortic aneurysm.
Ko Okumura - One of the best experts on this subject based on the ideXlab platform.
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Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in Aortic Tissue with Takayasu's arteritis.
Journal of vascular research, 2004Co-Authors: Yoshinori Seko, Kazuyuki Sugishita, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Ryozo NagaiAbstract:To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in Aortic Tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in Aortic Tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the Aortic Tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the Aortic Tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated Aortic Tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.
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Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in the Aortic Tissue of a patient with atherosclerotic Aortic aneurysm.
International angiology : a journal of the International Union of Angiology, 1998Co-Authors: Yoshinori Seko, Osamu Sato, Hideo Yagita, Ko Okumura, A Takagi, Takahashi N, Yoshio YazakiAbstract:We report a rare case of an atherosclerotic Aortic aneurysm with lymphocyte infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage was restricted. Immunohistochemical studies showed that the infiltrating cells mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and 65-kD heat-shock protein (HSP-65) was not strongly expressed in the Aortic Tissue. Although the immunohistochemical data were consistent with an ordinary atherosclerotic Aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune mechanism was involved in the pathogenesis of this case similar to Takayasu's arteritis, in which massive infiltration of delta T lymphocytes and strong expression of HSP-65 in the Aortic Tissue are characteristic.
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Perforin-secreting killer cell infiltration in the Aortic Tissue of patients with atherosclerotic Aortic aneurysm.
Japanese circulation journal, 1997Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Cell-mediated immunity has been implicated in the pathogenesis of vascular cell injury in patients with atherosclerotic Aortic aneurysms. To clarify the immunologic mechanisms involved, we examined the expression of a cytolytic factor, perforin, in infiltrating cells from Aortic Tissue samples taken from 6 patients with atherosclerotic Aortic aneurysms. Immunohistochemical studies showed that the infiltrating cells consisted mainly of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and T helper cells, and that perforin was expressed in NK cells and CTLs. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly on to the surface of arterial vascular cells. These findings provide the first direct evidence that some of the infiltrating cells in the Aortic Tissue consist of killer cells, and strongly suggest that these killer cells, especially NK cells and CTLs, may play a critical role in the vascular cell injury caused by atherosclerotic Aortic aneurysm by releasing perforin.
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Restricted Usage of T-Cell Receptor Vα-Vβ Genes in Infiltrating Cells in Aortic Tissue of Patients With Takayasu’s Arteritis
Circulation, 1996Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Background Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu’s arteritis. Methods and Results To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu’s arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Vα and Vβ genes in infiltrating cells in the Aortic Tissue of patients with Takayasu’s arteritis and atherosclerotic Aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Vα as well as Vβ gene transcripts in Takayasu’s arteritis were restricted. The infiltrating cells expressing Vα2, Vα16, Vα17, Vβ7, and Vβ13.1 were found in 3 of 4 patients. In contrast, TCR Vα-Vβ repertoires in atherosclerotic Aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gene expression between the two diseases. Conclusions The restricted usage of TCR Vα as well as Vβ genes by infiltrating T cells in Takayasu’s arteritis may indicate that a specific antigen in the Aortic Tissue was targeted. Our findings provide the evidence that distinct immunological mechanisms are involved in the pathogenesis of Takayasu’s arteritis and atherosclerotic Aortic aneurysm.
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perforin secreting killer cell infiltration and expression of a 65 kd heat shock protein in Aortic Tissue of patients with takayasu s arteritis
Journal of Clinical Investigation, 1994Co-Authors: Yoshinori Seko, Hideo Yagita, Ko Okumura, S Minota, Akemi Kawasaki, Yoichi Shinkai, K Maeda, O Sato, A Takagi, Yusuke TadaAbstract:Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of Aortic Tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the Aortic Tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the Aortic Tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the Aortic Tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.
Hideo Yagita - One of the best experts on this subject based on the ideXlab platform.
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Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in Aortic Tissue with Takayasu's arteritis.
Journal of vascular research, 2004Co-Authors: Yoshinori Seko, Kazuyuki Sugishita, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Ryozo NagaiAbstract:To further investigate the immunological mechanisms involved, we analyzed the expression of costimulatory molecules in Aortic Tissue and their counterpart molecules on infiltrating cells of patients with Takayasu's arteritis. We also examined the expression of major histocompatibility complex (MHC) class I chain-related (MIC) A in Aortic Tissue, which is known to be induced by external stress, and its counterpart NKG2D receptors on infiltrating cells. Among these costimulatory molecules, strong expression of 4-1BBL and Fas was induced in the Aortic Tissue, and most of the infiltrating cells expressed 4-1BB and FasL, suggesting these pathways play critical roles in T-cell-mediated vascular injury. We also found that MICA was strongly induced in the Aortic Tissue and that at least part of the infiltrating cells expressed NKG2D receptors. Some infiltrating cells - but not vascular smooth muscle cells - seemed to have undergone apoptosis. Our findings strongly suggest that 4-1BB/4-1BBL and Fas/FasL pathways play important roles in vascular injury in Takayasu's arteritis. We assume that gammadelta T cells infiltrated Aortic Tissue recognizing MICA, resulting in the induction of MHC antigens and costimulatory molecules, and then alphabeta T-cells infiltrated recognizing some auto-antigens presented by MHC antigens, leading to chronic inflammation.
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Restricted usage of T-cell receptor Valpha-Vbeta genes in infiltrating cells in the Aortic Tissue of a patient with atherosclerotic Aortic aneurysm.
International angiology : a journal of the International Union of Angiology, 1998Co-Authors: Yoshinori Seko, Osamu Sato, Hideo Yagita, Ko Okumura, A Takagi, Takahashi N, Yoshio YazakiAbstract:We report a rare case of an atherosclerotic Aortic aneurysm with lymphocyte infiltration in which T-cell receptor (TCR) Valpha as well as Vbeta gene usage was restricted. Immunohistochemical studies showed that the infiltrating cells mainly consisted of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells, and that there were almost no infiltrating delta T lymphocytes, and human leukocyte antigen (HLA) class I and 65-kD heat-shock protein (HSP-65) was not strongly expressed in the Aortic Tissue. Although the immunohistochemical data were consistent with an ordinary atherosclerotic Aortic aneurysm, in which TCR Valpha-Vbeta gene usage is known to be polyclonal, the restricted TCR gene usage suggests that a certain autoimmune mechanism was involved in the pathogenesis of this case similar to Takayasu's arteritis, in which massive infiltration of delta T lymphocytes and strong expression of HSP-65 in the Aortic Tissue are characteristic.
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Perforin-secreting killer cell infiltration in the Aortic Tissue of patients with atherosclerotic Aortic aneurysm.
Japanese circulation journal, 1997Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Cell-mediated immunity has been implicated in the pathogenesis of vascular cell injury in patients with atherosclerotic Aortic aneurysms. To clarify the immunologic mechanisms involved, we examined the expression of a cytolytic factor, perforin, in infiltrating cells from Aortic Tissue samples taken from 6 patients with atherosclerotic Aortic aneurysms. Immunohistochemical studies showed that the infiltrating cells consisted mainly of macrophages, natural killer (NK) cells, cytotoxic T lymphocytes (CTLs), and T helper cells, and that perforin was expressed in NK cells and CTLs. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly on to the surface of arterial vascular cells. These findings provide the first direct evidence that some of the infiltrating cells in the Aortic Tissue consist of killer cells, and strongly suggest that these killer cells, especially NK cells and CTLs, may play a critical role in the vascular cell injury caused by atherosclerotic Aortic aneurysm by releasing perforin.
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Restricted Usage of T-Cell Receptor Vα-Vβ Genes in Infiltrating Cells in Aortic Tissue of Patients With Takayasu’s Arteritis
Circulation, 1996Co-Authors: Yoshinori Seko, Osamu Sato, Atsuhiko Takagi, Yusuke Tada, Hiroshi Matsuo, Hideo Yagita, Ko Okumura, Yoshio YazakiAbstract:Background Infiltration by perforin-secreting killer lymphocytes, such as T cells and natural killer cells, has been shown to be involved in the pathogenesis of vascular cell damage in Takayasu’s arteritis. Methods and Results To investigate the immunological mechanisms involved, especially the nature of T-cell infiltration in Takayasu’s arteritis as well as atherosclerosis, we analyzed the expression of T-cell receptor (TCR) Vα and Vβ genes in infiltrating cells in the Aortic Tissue of patients with Takayasu’s arteritis and atherosclerotic Aortic aneurysm by polymerase chain reaction (PCR). We also analyzed the expression of cytokine genes by PCR. We found that the repertoires of TCR Vα as well as Vβ gene transcripts in Takayasu’s arteritis were restricted. The infiltrating cells expressing Vα2, Vα16, Vα17, Vβ7, and Vβ13.1 were found in 3 of 4 patients. In contrast, TCR Vα-Vβ repertoires in atherosclerotic Aortic aneurysm were polyclonal. There was no significant difference in the pattern of cytokine gene expression between the two diseases. Conclusions The restricted usage of TCR Vα as well as Vβ genes by infiltrating T cells in Takayasu’s arteritis may indicate that a specific antigen in the Aortic Tissue was targeted. Our findings provide the evidence that distinct immunological mechanisms are involved in the pathogenesis of Takayasu’s arteritis and atherosclerotic Aortic aneurysm.
-
perforin secreting killer cell infiltration and expression of a 65 kd heat shock protein in Aortic Tissue of patients with takayasu s arteritis
Journal of Clinical Investigation, 1994Co-Authors: Yoshinori Seko, Hideo Yagita, Ko Okumura, S Minota, Akemi Kawasaki, Yoichi Shinkai, K Maeda, O Sato, A Takagi, Yusuke TadaAbstract:Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of vascular cell injury in Takayasu's arteritis. To clarify the immunological mechanisms involved, we examined the expression of a cytolytic factor, perforin in infiltrating cells of Aortic Tissue samples from seven patients with Takayasu's arteritis. We also examined the expression of a 65-kD heat-shock protein (HSP-65), human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 in the Aortic Tissue. Immunohistochemical studies showed that the infiltrating cells mainly consisted of gamma delta T lymphocytes, natural killer cells, macrophages, cytotoxic T lymphocytes and T helper cells, and that perforin was expressed in gamma delta T lymphocytes, natural killer cells, and cytotoxic T lymphocytes. In situ hybridization analysis also revealed expression of perforin mRNA in the infiltrating cells. Immunoelectron microscopic studies demonstrated that the infiltrating cells released massive amounts of perforin directly onto the surface of arterial vascular cells. We also found that expression of HSP-65, human leukocyte antigen classes I and II, and intercellular adhesion molecule-1 was strongly induced in the Aortic Tissue and might facilitate the recognition, adhesion and cytotoxicity of the infiltrating killer lymphocytes. These findings provide the first direct evidence that the infiltrating cells in the Aortic Tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin.