Triggiani M, De Marino V, Sofia M, Faraone S, Ambrosio G, Carratù L, Marone G
Division of Clinical Immunology and Allergy, University of Naples Federico II, Italy.
Am J Respir Crit Care Med. 1997 Jul;156(1):94-100. doi: 10.1164/ajrccm.156.1.9608084.
Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.
血小板活化因子（PAF）是人类气道在急性和慢性炎症性肺部疾病期间产生的一种介质。PAF的水平受乙酰水解酶（AH）调节，该酶可将PAF转化为溶血PAF。为了确定人类支气管肺泡灌洗（BAL）液中是否存在AH，从正常供体（n = 18）以及患有轻度支气管哮喘的成年患者（n = 15）或肺纤维化患者（n = 15）中获取BAL液。在无细胞的BAL液中始终能检测到AH活性。BAL - AH是一种不同于分泌型磷脂酶A2、血浆AH和红细胞AH的酶。此外，暴露于产生活性氧的系统（黄嘌呤/黄嘌呤氧化酶）后，BAL - AH的活性被抑制高达95%。BAL - AH与BAL巨噬细胞数量显著相关（rs = 0.63；p < 0.02）。此外，BAL巨噬细胞在肿瘤坏死因子 - α（TNF - α）（100 ng/ml）刺激后以及自发地释放AH。支气管哮喘患者的BAL - AH活性（将PAF转化为溶血PAF的量为1.32±0.18 pmol/分钟）显著低于正常供体（2.25±0.26 pmol/分钟；p < 0.001）。相反，肺纤维化患者的BAL - AH活性（6.13±0.81 pmol/分钟）高于正常供体（p < 0.01）。支气管哮喘或肺纤维化患者BAL - AH活性的变化分别是由于活性分子数量的减少和增加，而非酶亲和力的改变。这些数据表明，人类BAL液含有一种细胞外AH活性，可使气道中释放的PAF失活。BAL - AH由肺泡巨噬细胞分泌，对活性氧诱导的损伤高度敏感。BAL - AH的分泌和失活可能会影响急性和慢性炎症性肺部疾病期间BAL液中该酶的水平，并最终调节这些疾病中PAF的促炎活性。
