Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis
Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis
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DOI：
10.1183/09031936.98.11010104
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发表时间：
1998-01-01
影响因子：
24.3
通讯作者：
Matsukura, S
中科院分区：
文献类型：
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作者：
Ashitani, J;Mukae, H;Matsukura, S
人中性粒细胞在嗜天青颗粒中含有三种抗菌肽和细胞毒性肽，它们属于哺乳动物中性粒细胞肽家族，称为防御素，我们研究了这些肽在弥漫性泛细支气管炎（DPB）中的作用。用放射免疫法测定30例DPB患者支气管肺泡灌洗液（BALF）中人中性粒细胞肽（HNP-1、HNP-2、HNP-3）含量，16例特发性肺纤维化（IPF）患者和健康成人，DPB患者BALF中防御素浓度高于IPF患者和健康受试者，DPB和IPF患者血浆防御素浓度也显著高于对照组。BALF中防御素浓度与中性粒细胞计数和白细胞介素-L浓度呈显著正相关。免疫组化显示，4例DPB患者的开放肺活检标本中的防御素定位于气道中的中性粒细胞和粘液性渗出物以及细支气管上皮细胞表面。fn体外研究表明，用佛波醇肉豆蔻酸醋酸酯、N-甲酰基-甲硫氨酰-亮氨酰-苯乙胺和人重组IL-8刺激中性粒细胞后，防御素的细胞外释放增强。用大环内酯类药物治疗DPB 6个月显着降低中性粒细胞计数以及BALF中防御素和IL-8的浓度。我们的结果表明，中性粒细胞来源的防御素在弥漫性泛细支气管炎的气道中积聚，提示防御素可能是该病中性粒细胞活性的标志物。
Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins, sere we investigate the role of these peptides in diffuse panbronchiolitis (DPB).Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and If healthy adults,The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects, DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls,In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-L. Immnunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. fn vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8, Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF.Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.