NEUTROPHILIC ALVEOLITIS IN IDIOPATHIC PULMONARY FIBROSIS - THE ROLE OF INTERLEUKIN-8
NEUTROPHILIC ALVEOLITIS IN IDIOPATHIC PULMONARY FIBROSIS - THE ROLE OF INTERLEUKIN-8
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DOI：
10.1164/ajrccm/145.6.1433
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发表时间：
1992-06-01
期刊：
影响因子：
--
通讯作者：
STRIETER, RM
中科院分区：
文献类型：
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作者：
LYNCH, JP;STANDIFORD, TJ;STRIETER, RM
特发性肺纤维化是一种免疫介导的肺部疾病，其中活化的肺泡巨噬细胞（AM）和中性粒细胞在炎性肺损伤的发病机制中起主要作用。导致嗜酸性肺泡炎的诱发和持续的因素尚不清楚。最近，一种新的细胞因子（白细胞介素-8）被描述为激活的单核吞噬细胞和各种其他类型的细胞释放，它表现出强大的趋化活性的多形核白细胞（PMN）。IL-8的表达增加已在以嗜中性粒细胞浸润为特征的其他炎性疾病中得到描述，包括银屑病、类风湿性关节炎和脓毒症综合征，但没有研究在间质性肺疾病的背景下评估这种细胞因子。我们之前已经证明，正常人AM在适当的刺激下会释放IL-8，但缺乏评估人AM在特定肺部疾病状态下表达IL-8的数据。在这项研究中，我们研究了IL-8的稳态mRNA表达的人肺泡巨噬细胞获得支气管肺泡灌洗（BAL）从特发性肺纤维化（IPF）或结节病患者和健康志愿者。因为它是已知的，坚持塑料培养板可能上调IL-8的基因表达在没有额外的刺激，我们提取的mRNA立即从细胞团获得的BAL，而不是使用培养的肺泡巨噬细胞单层。采用北方印迹法检测IL-8 mRNA的表达。我们发现IPF患者的BAL细胞组成性表达IL-8 mRNA，IL-8 mRNA的量（通过激光密度测定法评估）与BAL上中性粒细胞的百分比相关。相反，从健康受试者分离的BAL细胞不能组成性表达IL-8的mRNA，而在肺结节病患者中仅检测到低水平的IL-8 mRNA。IPF患者中IL-8 mRNA表达增强的细胞来源似乎是AM，因为从IPF患者中分离的AM组成性表达细胞相关蛋白，而来自结节病患者和健康受试者的AM产生的免疫反应性IL-8的量显著较少。这些数据表明，IL-8表达增加可能是IPF的一个特征，并支持IL-8在IPF的嗜酸性肺泡炎中的作用。
Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine In the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL. By contrast, BAL cells isolated from healthy subjects failed to express mRNA for IL-8 constitutively, whereas only low levels of IL-8 mRNA were detected in patients with pulmonary sarcoidosis. The cellular source of the augmented expression of IL-8 mRNA in patients with IPF appeared to be AM, as AM isolated from IPF patients constitutively expressed cell-associated protein, whereas AM from patients with sarcoidosis and healthy subjects produced significantly lesser quantities of immunoreactive IL-8. These data suggest that increased expression of IL-8 may be a feature of IPF and support a role for IL-8 in the neutrophilic alveolitis of IPF.