Anti-inflammatory potency of cellulose acetate beads by removing activated granulo/monocytes in ulcerative colitis

醋酸纤维素珠通过去除溃疡性结肠炎中活化的粒细胞/单核细胞而发挥抗炎作用

• 批准号: 08557039
• 负责人: ASAKURA Hitoshi
• 金额: $ 6.14万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557039/
• 关键词: Ulcerative colitis; Therapy; Granulo; monocyte apheresis; Leucocytapheresis; Activated platelets; DSS colits; 漬瘍性大腸炎; 酢酸セルローズビーズ; 顆粒球・単球除去療法; サイトカイン; 内皮細胞; 酢酸セルロースビーズ

Extracorporeal immunomodulation is thought to be secure therapy and we attempted to investigate the mechanisms that how granulo/monocyte apheresis (GOAP) using cellulose acetate beads (G-1) column can modulate the local inflammation in the treatment of ulcerative colitis (UC).At first, we investigated the feature of granulo/monocyte reactivity to the human umbilical vein endothelial cells and G-l beads. The circulating granulo/monocytes in patients with UC were generally activated and produce proinflammatory cytokines in response to the activated vascular endothelial cells. This could be responsible for the development and prolongation of the inflammation of ulcerative colitis. And we concluded that G-1 beads remove those activated cells and may improve the UC.However, complete depletion of neutrophils in rats improved the dextran sulphate sodium-induced colitis only in part. And inhibition of MOP-1 chemokine in rats did not improved the DSS induced colitis. These results implied that … More only the depression of neutrophils and monocytes did not improve the local inflammation of ulcerative colitis.At the time, the effects of leucocytapheresis (LCAP), another extracorporeal immuno-modulation system which removes all white blood cells (WBC), were compared with GCAIP on the induction therapy of UC.LOAP was more effective in the treatment of UC than GOAP.And LOAP was effective even on steroid-resistant ulcerative colitis. This clinical observation suggested that removing factor (s) other than granulocytes and monocytes improve the inflammation of UC.Hence changes of lymphocyte subsets and the influence of humorl factors on the adhesion of WBC to activated HUVEC were examined in LCAP therapy. But no signficant results were observed. Then we suspected platelets of the development of inflammation. Activated platelets were significantly increased in UC.Platelets from UC showed higher increasing effect on ROM production by indicator granulocytes than platelets from controls. Now we consider that removing activated platelets plays the fundamental role in the LCAP therapy. Less

体外免疫调节被认为是治疗溃疡性结肠炎（UC）的一种安全的方法，本研究旨在探讨使用醋酸纤维素珠（G-1）柱的颗粒/单核细胞单采术（GOAP）在治疗UC中调节局部炎症的机制。UC患者的循环颗粒/单核细胞通常被激活，并产生促炎细胞因子以响应激活的血管内皮细胞。这可能是溃疡性结肠炎炎症发展和延长的原因。我们的结论是，G-1珠去除这些活化的细胞，并可能改善UC。然而，在大鼠中，完全耗尽中性粒细胞仅部分改善葡聚糖硫酸钠诱导的结肠炎。抑制MOP-1趋化因子对DSS诱导的大鼠结肠炎无明显改善作用。这些结果表明， ...更多信息 同时，将另一种体外免疫调节系统--白细胞分离术（leucocytapheresis，LCAP）与GCAIP在诱导治疗溃疡性结肠炎中的作用进行了比较，LOAP对UC的治疗效果优于GOAP，LOAP对激素抵抗的溃疡性结肠炎也有效。临床观察表明，清除粒细胞和单核细胞以外的因子可改善UC的炎症反应。因此，在LCAP治疗中，观察了淋巴细胞亚群的变化以及体液因子对WBC与活化HUVEC粘附的影响。但未观察到显著结果。然后我们怀疑血小板的发展炎症。UC患者活化血小板显著增加，UC患者血小板对指示粒细胞ROM生成的增加作用高于对照组。目前认为，清除活化血小板是LCAP治疗的基础。少

项目成果

杉村一仁,柏木伸二,他: "消化器病up to date,consensus & controversies,1996" 永井書店, 127-130 (1997)

Kazuhito Sugimura、Shinji Kashiwagi 等人：“最新胃肠道疾病、共识与争议，1996” Nagai Shoten，127-130 (1997)

朝倉 均,杉村一仁,古川浩一: "慢性炎症性腸疾患IBDとステロイド療法" 臨床と研究. 74. 39-44 (1997)

Hitoshi Asakura、Kazuhito Sugimura、Koichi Furukawa：“慢性炎症性肠病 IBD 和类固醇治疗”临床与研究。74. 39-44 (1997)。

朝倉 均: "小林絢三編 消化器病 up to date" 永井書店(大阪), 396 (1997)

朝仓仁：《最新的消化系统疾病，小林健三主编》永井书店（大阪），396（1997）

船越和博,朝倉 均 他5名: "クローン病と潰瘍性大腸炎の腸粘膜病変におけるサイトカイン遺伝子発現のスペクトラム" Digestion. 59. 73-78 (1998)

Kazuhiro Funakoshi、Hitoshi Asakura 等 5 人：“克罗恩病和溃疡性结肠炎肠粘膜病变中的细胞因子基因表达谱”消化，59. 73-78 (1998)。

Hitoshi Asakura, Terasu Honma: "Concept and pathogenesis of inflammatory." Shokakigeka. 20. 25-32 (1997)

Hitoshi Asakura、Terasu Honma：“炎症的概念和发病机制。”