胰腺炎相关蛋白可保护肺免受白细胞诱导的损伤。

Pancreatitis-associated protein protects the lung from leukocyte-induced injury.

作者信息

Heller A, Fiedler F, Schmeck J, Lück V, Iovanna J L, Koch T

机构信息

Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden Germany.

出版信息

Anesthesiology. 1999 Nov;91(5):1408-14. doi: 10.1097/00000542-199911000-00034.

DOI:10.1097/00000542-199911000-00034

PMID:10551593

Abstract

BACKGROUND

Severe pancreatitis is often complicated by shock and acute lung failure. Little is known about the pathophysiologic impact of the 16.6-kD lectine, named pancreatitis-associated protein (PAP), which is expressed during pancreatitis and which reduces mortality in a rat model with severe pancreatitis. Therefore, the aim of this study was to investigate the effects of PAP on the pulmonary vasculature after leukocyte activation with N-formyl-Met-Leu-Phe (fMLP).

METHODS

The experiments were performed in buffer-perfused isolated rabbit lungs. Mean pulmonary artery pressure, weight gain, and thromboxane A2 synthesis of the lungs were monitored. PAP was obtained by affinity chromatography of pancreas juice from pancreatitic rats. The authors tested whether treatment with PAP (260 microg/l, n = 9; or 500 microg/l, n = 6) before fMLP injection (10(-6) M) influences mean pulmonary artery pressure and edema formation. Lungs that were treated only with fMLP (n = 6) served as controls. Additional experiments in which PAP was applied were performed to study whether PAP (260 microg/l, n = 3; 500 microg/l, n = 3; 1,000 microg/l, n = 3) itself effects lung vasculature.

RESULTS

Application of fMLP resulted in an increase of mean pulmonary artery pressure (+/- SD) from 8 +/- 2 mmHg up to 26 +/-13 mmHg (P < 0.01) at a flow of 150 ml/min. Pretreatment with PAP reduced the peak pressure developed after fMLP to 15 +/- 7 mmHg (PAP 260 microg/l; P < 0.05) and to 9 +/- 4 mmHg (PAP 500 microg/l), respectively. In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration. In parallel to the attenuated pressure increase, thromboxane A2 release was significantly suppressed in the 260-microg/l (200 +/- 220 pmol x ml(-1) x min(-1); P < 0.01) and 500-microg/l (285 +/- 70 pmol x m(-1) x min(-1); P < 0.05) PAP groups compared with controls (1,138 +/- 800 pmol x ml(-1) x mi(-1)). Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release.

CONCLUSION

Clinically relevant concentrations of PAP prevented fMLP-induced vasoconstriction and edema formation in the lung. These findings point toward a protective effect of PAP on polymorphonuclear neutrophil leukocyte-mediated lung injury.

摘要

背景

重症胰腺炎常并发休克和急性肺衰竭。对于一种名为胰腺炎相关蛋白（PAP）的16.6-kD凝集素在胰腺炎期间表达且能降低重症胰腺炎大鼠模型死亡率的病理生理影响，人们了解甚少。因此，本研究旨在探讨PAP对用N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）激活白细胞后肺血管系统的影响。

方法

实验在缓冲液灌注的离体兔肺上进行。监测平均肺动脉压、肺重量增加及肺血栓素A2合成。PAP通过对胰腺炎大鼠胰液进行亲和层析获得。作者测试在注射fMLP（10⁻⁶ M）前用PAP（260 μg/l，n = 9；或500 μg/l，n = 6）处理是否会影响平均肺动脉压和水肿形成。仅用fMLP处理的肺（n = 6）作为对照。进行了应用PAP的额外实验，以研究PAP（260 μg/l，n = 3；500 μg/l，n = 3；1000 μg/l，n = 3）本身对肺血管系统的影响。

结果

在150 ml/min的流量下，应用fMLP导致平均肺动脉压（±标准差）从8 ± 2 mmHg升高至26 ± 13 mmHg（P < 0.01）。用PAP预处理可将fMLP后出现的峰值压力分别降至15 ± 7 mmHg（PAP 260 μg/l；P < 0.05）和9 ± 4 mmHg（PAP 500 μg/l）。此外，两种浓度的PAP预处理均在150分钟后防止了fMLP诱导的对照组肺重量增加9 ± 7 g。与压力升高减弱平行，在260 μg/l（200 ± 220 pmol·ml⁻¹·min⁻¹；P < 0.01）和500 μg/l（285 ± 70 pmol·m⁻¹·min⁻¹；P < 0.05）PAP组中，血栓素A2释放与对照组（1138 ± 800 pmol·ml⁻¹·mi⁻¹）相比显著受到抑制。单独用任何一种浓度的PAP处理均未引起平均肺动脉压、重量增加或血栓素A2释放的任何变化。