Werner J, Z'graggen K, Fernández-del Castillo C, Lewandrowski K B, Compton C C, Warshaw A L
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Ann Surg. 1999 Jun;229(6):834-40; discussion 841-2. doi: 10.1097/00000658-199906000-00010.
To analyze the time points and levels of the expression of adhesion molecules in the pancreas and lung in pancreatitis of different severities, and to assess whether treatment with a monoclonal antibody against intercellular adhesion molecule-1 (ICAM-1) can reduce local and systemic complications.
The outcome of severe acute pancreatitis relates to its pulmonary and septic complications. Leukocyte adhesion and infiltration, both mediated by ICAM-1, are central events in the pathogenesis of necrotizing pancreatitis.
Expression of ICAM-1 at different time points was assessed by immunohistochemistry and Western blot analysis in pancreas and lungs from rats with mild edematous or severe necrotizing pancreatitis. ICAM-1 expression was correlated with leukocyte infiltration and histologic changes. The possible therapeutic effect of monoclonal antibodies against ICAM-1 was assessed by measuring pancreatic and lung injury.
In edematous pancreatitis, increased ICAM-1 expression in pancreas was evident by 6 hours but did not occur in lung. In contrast, ICAM-1 was upregulated at 3 hours in the pancreas and at 12 hours in lung in necrotizing pancreatitis. Increased expression of ICAM-1 preceded leukocyte infiltration. Treatment of severe necrotizing pancreatitis with monoclonal antibodies against ICAM-1 decreased both local pancreatic injury and systemic lung injury compared with untreated controls.
Upregulation of ICAM-1 and subsequent leukocyte infiltration appear to be significant mediators of pancreatic and pulmonary injury in pancreatitis, and both the onset and extent correlate with severity. The time course should permit effective prevention of tissue damage by treatment with ICAM-1 antibodies.
分析不同严重程度胰腺炎时胰腺和肺组织中黏附分子表达的时间点及水平，并评估抗细胞间黏附分子-1（ICAM-1）单克隆抗体治疗能否减少局部和全身并发症。
重症急性胰腺炎的预后与其肺部和感染性并发症相关。由ICAM-1介导的白细胞黏附和浸润是坏死性胰腺炎发病机制中的关键事件。
采用免疫组织化学和蛋白质印迹分析评估轻度水肿性或重症坏死性胰腺炎大鼠胰腺和肺组织中不同时间点ICAM-1的表达。将ICAM-1表达与白细胞浸润及组织学变化相关联。通过测量胰腺和肺损伤评估抗ICAM-1单克隆抗体的可能治疗效果。
在水肿性胰腺炎中，胰腺ICAM-1表达在6小时时明显增加，但肺组织未出现这种情况。相比之下，在坏死性胰腺炎中，胰腺ICAM-1在3小时时上调，肺组织在12小时时上调。ICAM-1表达增加先于白细胞浸润。与未治疗的对照组相比，用抗ICAM-1单克隆抗体治疗重症坏死性胰腺炎可减轻局部胰腺损伤和全身肺损伤。
ICAM-1上调及随后的白细胞浸润似乎是胰腺炎中胰腺和肺损伤的重要介质，其发生时间和程度均与严重程度相关。该时间进程应允许通过ICAM-1抗体治疗有效预防组织损伤。
