A Novel Diamino-Pyridine Derivative Prevents Excessive Leukocyte Infiltration in Aggravation of Acute Necrotizing Pancreatitis
A Novel Diamino-Pyridine Derivative Prevents Excessive Leukocyte Infiltration in Aggravation of Acute Necrotizing Pancreatitis
复制标题
一种新型二氨基吡啶衍生物可防止白细胞过度浸润导致急性坏死性胰腺炎恶化
作者：
J. Yamauchi;M. Sunamura;K. Shibuya;K. Takeda;M. Kobari;S. Matsuno
胰腺中的白细胞浸润参与急性胰腺炎从水肿期到坏死变化以及从轻度疾病到重度疾病的恶化;然而，负责白细胞积聚的机制尚未完全了解。本研究旨在阐明白细胞积聚到胰腺的机制，并阐明一种新的二氨基吡啶衍生物，IS-741对白细胞-内皮细胞相互作用的治疗效果，使用大鼠坏死性胰腺炎模型。在坏死性胰腺炎动物中，通过体内荧光显微镜评估的粘附于胰腺集合小静脉的白细胞数量以时间依赖性方式显著增加。通过流式细胞术分析确定的循环中性粒细胞上的CD 11b表达在2 h后增强至约500%。IS-741显著减弱了白细胞粘附，伴随着较低的CD 11b上调。这些发现进一步得到组织学检查的支持，即胰腺中白细胞的积累被IS-741显著抑制。这些结果表明，在急性坏死性胰腺炎的早期阶段的白细胞积聚可能是介导的白细胞-内皮细胞的相互作用，通过白细胞整合素CD 11b/18。IS-741由于其对CD 11b上调的抑制作用而减弱了白细胞与内皮细胞的相互作用。
Leukocyte infiltration in the pancreas is involved in the aggravation of acute pancreatitis from edematous phase into necrotic change, and mild disease into severe disease; however, the mechanism responsible for leukocyte accumulation is not fully understood. This study was designed to clarify the mechanism underlying leukocyte accumulation into the pancreas and to elucidate the therapeutic efficacy of a novel diamino-pyridine derivative, IS-741 on leukocyte-endothelial cell interaction using rat necrotizing pancreatitis model. The number of adherent leukocytes to pancreatic collecting venules assessed by in vivo fluorescence microscopy increased significantly in necrotizing pancreatitis animals in a time-dependent manner. The expression of CD11b on circulating neutrophils determined by flow cytometric analysis was enhanced to approximately 500% after 2 h. IS-741 attenuated the leukocyte adherence significantly, accompanied by a lower up-regulation of CD11b. These findings were further supported by the histological examination that the accumulation of leukocytes in the pancreas was remarkably inhibited by IS-741. These results suggest that the leukocyte accumulation in the early phase of acute necrotizing pancreatitis may be mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. IS-741 attenuated the leukocyte endothelial cell interaction as a consequence of its inhibitory effect on CD11b upregulation.
影响因子：
20.3
作者：
T. Carlos;J. Harlan
通讯作者：
T. Carlos;J. Harlan
前列腺素E1对雨蛙素诱导的急性胰腺炎大鼠急性肺损伤的保护作用。
DOI：
10.1152/ajpgi.1997.272.1.g23
发表时间：
1997
期刊：
The American journal of physiology
影响因子：
--
作者：
Yamanaka,K;Saluja,AK;Brown,GE;Yamaguchi,Y;Hofbauer,B;Steer,ML
通讯作者：
Steer,ML