Service of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland.
J Clin Pathol. 2011 May;64(5):387-93. doi: 10.1136/jcp.2010.088500. Epub 2011 Feb 23.
Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4.
The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining.
The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates.
These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.
急性胰腺炎是一种严重程度不同的炎症过程。白细胞被认为在胰腺炎和胰腺炎相关肺损伤的发展中起关键作用。炎症细胞及其介质之间的相互作用对于确定组织损伤至关重要。单核细胞趋化蛋白-1（或 CCL-2）、CCR-2 和 CCR-4 是参与白细胞迁移的趋化因子和趋化因子受体。本研究旨在评估 CCL-2、CCR-2 和 CCR-4 趋化因子受体在鹅膏蕈碱诱导的胰腺炎和胰腺炎相关肺损伤发病机制中的作用。为了研究吸引白细胞细胞进入炎症组织的 CCL-2、CCR-2 和 CCR-4 趋化因子受体的作用，在不表达 CCL-2、CCR-2 或 CCR-4 的小鼠中给予超最大剂量的鹅膏蕈碱诱导胰腺炎。
通过血清淀粉酶、胰腺水肿和腺泡细胞坏死来衡量胰腺炎的严重程度。通过评估肺微血管通透性和肺髓过氧化物酶活性来定量肺损伤。通过实时 PCR 定量趋化因子和趋化因子受体的表达。通过免疫染色研究浸润胰腺和肺部的炎症细胞的性质。
作者发现，在胰腺炎期间，胰腺 CCL-2 和 CCR-2 水平升高。在 CCL-2 缺乏的小鼠中，胰腺炎和相关的肺损伤均减弱，但并未完全预防，而 CCR-2 或 CCR-4 的缺乏并不减轻胰腺炎和肺损伤的严重程度。与 CCL-2 充足的同窝小鼠相比，CCL-2 缺乏的小鼠中中性粒细胞和单核细胞/巨噬细胞（MOMA）-2 细胞的数量明显减少。
这些结果表明，CCL-2 通过调节中性粒细胞和 MOMA-2 细胞的浸润在胰腺炎中起关键作用，其缺乏可能改善疾病的预后。
