Activated Leukocyte-Endothelium Interactions during Ischemia Cause Endothelial Dysfunction on Reperfusion.

缺血期间激活的白细胞-内皮相互作用导致再灌注时内皮功能障碍。

• 批准号: 07671460
• 负责人: ONODA Koji
• 金额: $ 1.41万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671460/
• 关键词: REPERFUSION INJURY; ADHESION MOLECULE; ENDOTHELIAL CELL; NEUTROPHIL; MONOCLONAL ANTIBODY; 虚血再潅流障害; 活性化酸素; 活性化酵素

Background. Injury due to reperfusion of ischemic heart or lung is mediated by leukocyte-endothelial cell interactions, dependent on the integrin CDl1b, CDl8, and its endothelial cell ligand intercellular adhesion molecule. We studied these interactions and tried to mitigate this injury with monoclonal antibodies directed against the integrins.Methods. The damage to endothelial cells exposed to ischemia and reperfusion was estimated by assessing the maximum relaxation rate of rat aortic or human pulmonary artery smooth muscle induced by endothelium-derived relaxing factor in the following groups. Group Ia : control. Group IIa : bovine leukocytes activated by PMA incubated with hypoxic bovine aortic endothelial cells (BEC). Group IIIa : bovine leikocytes activated by PMA which received monoclonal antibodies (MoAb) against CDl1b incubated with BEC.Group IVa : bovine leikocytes activated by PMA which received monoclonal antibodies (MoAb) against CDl8 incubated with BEC.Human pulmonary artery smooth muscle, human pulmonary artery endothelial cells in group Ib, IIb, IIIb, and IVb under similar conditions.Results. The maximum relaxation rate of bovine smooth muscle was 51.5<plus-minus>2.4% in group Ia. The rates in groups IIIa and IVa (24.1<plus-minus>3.7% and 20.8<plus-minus>2.5%) were significantly greater than in group IIa (8.9<plus-minus>1.3%, p<0.05). Futhermore, the maximum relaxation rate of human smooth muscle was 50.3<plus-minus>2.0% in group Ib. The rates in groups IIIb and IVb (40.9<plus-minus>1.0% and 41.8<plus-minus>1.7%) were significantly greater than in group IIb (19.7<plus-minusConclusions. Antibodies against CDl1b and CDl8 prevent reperfusion-induced lung injury mediated by neutrophil-endothelial cell interactions.

背景。缺血心脏或肺的再灌注损伤是由白细胞-内皮细胞相互作用介导的，依赖于整合素CDl1b、cdl18及其内皮细胞配体细胞间粘附分子。我们研究了这些相互作用，并试图用针对整合素的单克隆抗体减轻这种损伤。通过测定内皮源性舒张因子对各组大鼠主动脉或人肺动脉平滑肌的最大舒张率，评估缺血再灌注对内皮细胞的损伤程度。Ia组：对照组。IIa组：经PMA活化的牛白细胞与缺氧牛主动脉内皮细胞（BEC）孵育。IIIa组：经PMA活化的牛白细胞，接受抗cd11b单克隆抗体（MoAb）与BEC孵育。IVa组：经PMA活化的牛白细胞，接受抗cd18单克隆抗体（MoAb）与BEC孵育。相似条件下，Ib、IIb、IIIb、IVb组的人肺动脉平滑肌、人肺动脉内皮细胞。Ia组牛平滑肌最大松弛率为51.5<正负>2.4%。IIIa组和IVa组的发生率（24.1<正负>3.7%和20.8<正负>2.5%）显著高于IIa组（8.9<正负>1.3%,p<0.05）。Ib组人体平滑肌最大松弛率为50.3<正负>2.0%，IIIb组和IVb组（40.9<正负>1.0%和41.8<正负>1.7%）明显大于IIb组（19.7<正负）。抗CDl1b和CDl8抗体可预防中性粒细胞-内皮细胞相互作用介导的再灌注诱导的肺损伤。

项目成果

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Hironori Tenpaku 等人：“末端温停跳液对微管形态变化和心脏功能的影响。”

Yoshihiko Katayama et al.: "Effects of Inhaled Nitric Oxide in Single Lung Transplantation in Rats with Monocrotaline-induced Pulmonary Hypertension" J.Heart Lung Transplant. 14. 486-492 (1995)

Yoshihiko Katayama 等人：“吸入一氧化氮对野百合碱诱发肺动脉高压大鼠单肺移植的影响”J.心肺移植。

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Yoshihiko katayama：“吸入一氧化氮对百豆碱诱导的肺动脉高压大鼠单次长期移植的影响”《热与肺移植杂志》。