Schmekel B, Seveus L, Xu S Y, Venge P
Department of Medicine and Care, University Hospital, Linköping, Sweden.
Respir Med. 2000 Jun;94(6):564-8. doi: 10.1053/rmed.2000.0776.
Myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) are proteins which are stored in neutrophil granulocytes, in the primary and secondary granules, respectively. These granules or their contents of MPO and HNL are secreted upon activation of the cells, and measurement of these soluble markers in biological fluids, such as bronchoalveolar lavage (BAL), has been proposed to mirror the degree of neutrophil activity in the tissue. We conducted a BAL study in 10 healthy volunteers, with the aim to evaluate the intra-individual variability of the concentration of HNL and MPO recovered in sequential aspirations, during a time period when the concentrations of HNL and MPO in BAL fluids were considered to have equilibrated with those in the underlying tissues. The concentrations of HNL were less variable than those of MPO (coefficients of variability 0.33 +/- 0.07 vs. 0.92 +/- 0.28; P = 0.01), suggesting HNL to be a more useful marker of neutrophil activity within the airspace. The specificity of HNL as a selective index of neutrophil cells was confirmed by means of immunohistochemical staining of uninvolved lung tissue specimens obtained from patients referred to pulmonectomy due to carcinoma. While HNL was located only to intracellular spaces of neutrophils, MPO was in addition located to other cells as well. We speculate that the dynamic changes of pressure across the membranes and flow of solutes during a lavage process might mobilize particulate matter and adherent cells, some of which may be loaded with MPO, and that this may introduce larger variability in the recovery of MPO than of HNL. We conclude that using HNL as a soluble indicator of neutrophil presence is more feasible than using MPO.
髓过氧化物酶(MPO)和人中性粒细胞脂质运载蛋白(HNL)是分别储存在中性粒细胞初级和次级颗粒中的蛋白质。这些颗粒或其所含的MPO和HNL在细胞激活时会分泌出来,有人提议通过测量生物流体(如支气管肺泡灌洗(BAL)液)中这些可溶性标志物来反映组织中中性粒细胞的活性程度。我们对10名健康志愿者进行了BAL研究,目的是评估在BAL液中HNL和MPO浓度被认为已与潜在组织中的浓度达到平衡的时间段内,连续抽吸回收的HNL和MPO浓度的个体内变异性。HNL的浓度变异性低于MPO(变异系数分别为0.33±0.07和0.92±0.28;P = 0.01),这表明HNL是气腔内中性粒细胞活性更有用的标志物。通过对因癌症接受肺切除术患者的未受累肺组织标本进行免疫组织化学染色,证实了HNL作为中性粒细胞选择性指标的特异性。虽然HNL仅定位于中性粒细胞的细胞内空间,但MPO还定位于其他细胞。我们推测灌洗过程中跨膜压力和溶质流动的动态变化可能会动员颗粒物和黏附细胞,其中一些可能含有MPO,这可能导致MPO回收的变异性比HNL更大。我们得出结论,使用HNL作为中性粒细胞存在的可溶性指标比使用MPO更可行。