Clinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases.

It has previously been reported that the expression of monocyte chemoattractant protein-1 (MCP-1) in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF) was different from that in the tissues of patients with other interstitial lung diseases (ILDs). The aim of this study was to determine whether this difference reflects the amount of MCP-1 in the bronchoalveolar lavage fluid (BALF) or serum of patients with ILD, and whether such a correlation, if it exists, is clinically useful. MCP-1 concentrations in the BALF and sera were evaluated in 86 patients with ILDs including IPF, acute interstitial pneumonia, interstitial pneumonia with collagen vascular disease (IP-CVD), chronic interstitial pneumonia (CIP), bronchiolitis obliterans-organizing pneumonia, sarcoidosis, hypersensitivity pneumonitis, and in 10 normal healthy volunteers who were controls (NC). BALF MCP-1 levels were significantly elevated in the IPF, IP-CVD, CIP and sarcoidosis groups compared with the NC group. The level in the IPF group was significantly higher than that in any other patient group. Serum MCP-1 levels in the IPF, IP-CVD, CIP and sarcoidosis groups were significantly higher than the NC group. No statistical difference was found in serum MCP-1 levels between the IPF, IP-CVD and CIP groups. BALF MCP-1 levels were significantly higher than serum MCP-1 levels in the IPF group and lower than in the IP-CVD and CIP groups. Serum MCP-1 levels correlated with the clinical course of ILD treated with corticosteroid therapy. These results show that measurement of monocyte chemoattractant protein-1 levels in both bronchoalveolar lavage fluid and serum may be helpful in discriminating idiopathic pulmonary fibrosis from other types of interstitial lung disease and that monitoring of serum monocyte chemoattractant protein-1 may be useful for predicting the clinical course of interstitial lung diseases.     

Elevated BALF concentrations of alpha- and beta-defensins in patients with pulmonary alveolar proteinosis

Defensins are endogenous antibiotics and regulators of inflammation, immunity and wound repair. Their concentrations are substantially increased in bronchoalveolar lavage fluid (BALF) of patients with infectious lung diseases. alpha-defensin (HAD) levels are also elevated in patients with idiopathic pulmonary fibrosis (IPF) and correlated with the decline in pulmonary function tests, suggesting the association of defensins with the pathogenesis of interstitial lung diseases. The aim of this study was to determine the profile of defensins in interstitial lung diseases. Serum and BALF levels of HAD and beta-defensin 1 and 2 (HBD-1, and -2) were measured by radioimmunoassay in 63 patients with interstitial lung diseases, including idiopathic pulmonary alveolar proteinosis (PAP), IPF, nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) and pulmonary sarcoidosis, and in 9 healthy volunteers as controls. Levels of HAD in BALF of patients with PAP were significantly higher than those in controls and patients with COP and sarcoidosis. Serum levels of HAD in all groups were significantly higher than those in controls. Levels of HBD-1 and -2 in BALF of patients with PAP were extremely high in all subjects. Serum levels of HBD-1 were higher in all patient groups, with the exception of those with PAP, and those of HBD-2 were also higher in patients with IPF and sarcoidosis, compared with controls. BALF of PAP patients, but not IPF patients and controls, expressed antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Our findings suggest different kinetics of HAD and HBD-1 and -2 in serum and BALF of interstitial lung diseases and that these antimicrobial peptides in the airway lumen may contribute to prevention of bacterial airway infections in PAP.     

Usual interstitial pneumonia: idiopathic pulmonary fibrosis versus collagen vascular diseases

BACKGROUND: Bronchoalveolar lavage fluid (BALF) lymphocytosis was found in patients with usual interstitial pneumonia (UIP) associated with collagen vascular diseases (CVD) other than diffuse systemic sclerosis (SSc), but it was not found in patients with idiopathic pulmonary fibrosis (IPF), a disease histologically diagnosed as UIP. This difference could be partly due to variations of UIP spectrums between IPF and interstitial pneumonia associated with CVD. METHODS: We scored histopathological findings of lung specimens obtained from 31 cases (16 IPF, 9 CVD other than SSc and 6 SSc) using a semiquantitative scoring method. All cases were diagnosed as UIP by surgical lung biopsy. None of the patients were current smokers. RESULTS: Compared with IPF and SSc cases, CVD patients without SSc presented decreased scores of fibrosis (p < 0.01) and alveolar space cellularity (severity, p < 0.05). Lymphocytes were mainly localized in the alveolar walls and the majority of cells in the alveolar spaces were macrophages. On the other hand, other scores such as cellularity and alveolar wall cell infiltrate did not vary among these three groups. CONCLUSION: Fewer macrophages in the alveolar spaces and a decrease in the degree of fibrosis may contribute to BALF lymphocytosis more in patients with UIP/CVD non-SSc than in patients with IPF/UIP and UIP-SSc.     

Proteolytic activities in bronchoalveolar lavage fluid of interstitial lung diseases: correlation to stage and prognosis

In 18 patients with sarcoidosis, 10 patients with idiopathic pulmonary fibrosis (IPF), 6 patients with exogen allergic alveolitis (EAA), and 9 control persons we investigated proteolytic activities in bronchoalveolar lavage fluid (BALF). In lymphocyte-macrophage alveolitis (i.e. sarcoidosis and EAA) proteolytic activities in BALF were low, but the activities correlated with lung function deterioration within 1 year. In IPF (i.e. in neutrophil alveolitis) we found a striking correlation between proteolytic activities and stage of disease: high activities correlated with early stages, lower values with late stages of IPF. Measurement of proteolytic activity in BALF seems to be of interest to differential diagnosis and to prognosis of interstitial lung disease.     

Bronchoalveolar lavage fluid angiotensin-converting enzyme in interstitial lung diseases

In this study we evaluated the disease specificity of bronchoalveolar lavage fluid angiotensin-converting enzyme (BALF-ACE), its correlation with cellular constituents of bronchoalveolar lavage fluid (BALF), and for sarcoidosis, with other proposed markers of disease activity. Furthermore, the question of the clinical value of BALF-ACE determinations in in interstitial lung diseases or any of its subgroups was addressed. The study population consisted of 222 patients, 69 with biopsy proven sarcoidosis, 3 with hypersensitivity pneumonitis, 4 with acute histoplasmosis, 27 with idiopathic pulmonary fibrosis (IPF), 4 with rheumatoid arthritis-related interstitial fibrosis, 9 with pulmonary drug toxicity, 16 with pulmonary malignancies, 26 with other parenchymal lung disease entities, and 30 in whom the final diagnosis remained indeterminate. Elevated BALF-ACE concentrations were seen in all diagnostic categories. In sarcoidosis BALF-ACE levels correlated well with lavage lymphocyte counts (r = 0.49; p less than 0.0001), in contrast to IPF where they correlated well with lavage neutrophil counts (r = 0.51; p less than 0.007). The correlation of BALF-ACE and serum-ACE was significant. In sarcoidosis the mean BALF-ACE level was lower for patients with Stage-I chest roentgenographic patterns (0.664 U/L), compared to those with Stage II (1.112 U/L) and Stage III (1.083 U/L). It was concluded that elevated BALF-ACE levels are not specific for sarcoidosis. The correlations of BALF-ACE levels with different cellular constituents of BALF suggest a different cellular origin of BALF-ACE. In sarcoidosis BALF-ACE levels correlate well with other proposed markers of disease activity and seem to reflect pulmonary activity better than serum ACE.(ABSTRACT TRUNCATED AT 250 WORDS)     

间质性肺疾病患者血清和支气管肺泡灌洗液中内皮素1活性的变化

目的评价内皮素对肺纤维化发生、发展作用的影响。方法利用同位素放射免疫直接测定法,检测１０例肺结节病和８例特发性肺纤维化（ＩＰＦ）患者外周血和支气管肺泡灌洗液（ＢＡＬＦ）中内皮素１（ＥＴ１）的活性,并与８名健康非吸烟者进行对照。结果肺结节病和ＩＰＦ患者血清和ＢＡＬＦ中的ＥＴ１活性分别为（６２±２９）ｎｇ／Ｌ,（１７０±２４）ｎｇ／Ｌ和（７７±７１）ｎｇ／Ｌ、（１０±３）ｎｇ／Ｌ,与正常对照组（２０±８）ｎｇ／Ｌ、（４０±０６）ｎｇ／Ｌ比较,差异有显著性（Ｐ＜００１）;血清中ＥＴ１活性与动脉血氧分压（ＰａＯ２）呈明显负相关（ｒ＝－０５３８,Ｐ＜００１）;结节病组和ＩＰＦ组ＢＡＬＦ中的ＥＴ１水平与ＢＡＬＦ中细胞总数呈正相关（ｒ＝０６４９,Ｐ＜００１）,肺结节病患者、ＩＰＦ患者ＢＡＬＦ中ＥＴ１与淋巴细胞、中性粒细胞呈正相关（ｒ＝０７１２,０８１３,Ｐ均＜００１）。结论ＥＴ１在肺结节病和ＩＰＦ发病机制中起着重要作用,并可作为疾病活动性判定的一项重要参考指标。     

间质性肺疾病支气管肺泡灌洗液的酶活性研究

目的探讨支气管肺泡灌洗液（ＢＡＬＦ）多项酶活性与间质性肺疾病（ＩＬＤ）的关系。方法检测３０例ＩＬＤｓ：包括特发性肺纤维化（ＩＰＦ）１８例和结节病（Ｓａｒｃ）１２例与９例正常对照者的ＢＡＬＦ中超氧化歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、血管紧张素转换酶（ＡＣＥ）和乳酸脱氢酶（ＬＤＨ）活性，并分类计数ＢＡＬＦ细胞成份。结果（１）ＩＰＦ组ＢＡＬＦ中各项酶活性均与对照组间差异有显著性（ＳＯＤ和ＧＳＨ－ＰＸ降低，ＡＣＥ和ＬＤＨ升高）（Ｐ＜０．０５）；而Ｓａｒｃ组仅见ＡＣＥ明显增高（Ｐ＜０．０５）。（２）ＢＡＬＦ－ＡＣＥ与Ｓａｒｃ组淋巴细胞百分比及ＣＤ＋４／ＣＤ＋８比值均有显著线性相关（Ｐ＜０．０５）。结论ＢＡＬＦ中ＳＯＤ、ＧＳＨ－ＰＸ、ＡＣＥ和ＬＤＨ活性测定，有助于进一步探讨ＩＬＤ发病机理和提供辅助诊断依据，ＢＡＬＦ－ＡＣＥ对判断Ｓａｒｃ活动性有重要临床意义。     

A comparison of albumin and urea as reference markers in bronchoalveolar lavage fluid from patients with interstitial lung disease

Lavage fluids were investigated for 67 subjects in 6 groups: 12 with active sarcoidosis, 8 with inactive sarcoidosis, 17 with pigeon breeder's disease, 10 asymptomatic pigeon breeders, 12 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects. Albumin and urea per ml of bronchoalveolar lavage fluid (BALF) were determined for each subject together with percentage return of fluid (BAL%). Novel assay systems were employed to measure urea and albumin and these were compared with existing analytical techniques. When compared with the control group, we found that urea per ml of BALF was not statistically different for all other groups, except those with pigeon breeder's disease who had significantly raised levels. For albumin, however, three groups had significantly higher levels than the controls, namely those with active sarcoidosis, pigeon breeder's disease and IPF. BAL% return showed no significant differences for any group when compared with the controls. We conclude that since albumin is significantly raised in most patients with interstitial lung disease it does not represent a suitable marker for the quantitation of reactive proteins in BALF. Urea shows much less variability between groups than does albumin, and hence in the absence of a proven alternative represents the most reliable estimate available of epithelial lining fluid dilution during the lavage procedure, providing dwell time is kept to a minimum.     

Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease.

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.     

Increased procollagen III aminoterminal peptide-related antigens and fibroblast growth signals in the lungs of patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder characterized by an increased density of inflammatory cells, fibroblasts, and collagen within the lung parenchyma. To gain insights into the mechanisms leading to the increased density of fibroblasts and altered collagen metabolism in the IPF lung, bronchoalveolar lavage fluid from normal subjects and patients with IPF or sarcoidosis was analyzed for (1) the presence of antigenic material related to the aminoterminal propeptide domain of type III procollagen, and (2) fibroblast growth-promoting activity in the extracellular milieu of the lower respiratory tract. Whereas bronchoalveolar lavage fluid (BALF) type III procollagen aminoterminal peptide-related antigen levels in 59 patients with sarcoidosis were similar to the levels of control subjects (p greater than 0.10), 31 patients with IPF had markedly increased levels (12-fold over controls; p less than 0.025, IPF versus controls; p less than 0.01, IPF versus sarcoidosis). Type III procollagen aminoterminal peptide-related antigen levels correlated with an increase in the ability of BALF to stimulate fibroblast proliferation (p less than 0.05). Furthermore, BALF from patients with IPF markedly stimulated human lung fibroblast proliferation in vitro (199% increase, p less than 0.01), whereas lavage fluid from patients with sarcoidosis and from control subjects did not. The enhanced fibroblast proliferation induced by IPF BALF occurred in the absence of serum and exogenous growth factors, suggesting that both competence- and progression-type growth factors were present in the lavage fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histochemical evaluation of lung collagen content in acute and chronic interstitial diseases

The collagen content and its aggregational state was histochemically measured in interstitial lung diseases. Open chest biopsies of ten patients with adult respiratory distress syndrome, seven patients with sarcoidosis, and nine patients with fibrosis associated with connective tissue diseases and with idiopathic pulmonary fibrosis (IPF/CTD) were compared with eight samples of normal lungs. The collagen content of diseased lungs was significantly increased when compared to control lungs, but no difference was observed among the pathologic groups. The analysis of collagen aggregational state showed maximal aggregation in IPF/CTD, followed by sarcoidosis, ARDS, and control lungs, in decreasing order. The results suggest that measurement of collagen aggregation coupled with collagen content could be used in the evaluation of interstitial lung disease and encourage the use of new techniques in order to better explain the dramatic histologic and functional alterations observed in many disease-associated lung processes.     

CCR5 expression and CC chemokine levels in idiopathic pulmonary fibrosis.

CC chemokines play an important role in the pathogenetic mechanisms of interstitial lung disease, while a downregulation of CC chemokine receptor (CCR)5 in the fibrotic stages of sarcoidosis has been observed. To evaluate the involvement of CC chemokines and the expression of CCR5 in idiopathic pulmonary fibrosis (IPF) and, more specifically, in usual interstitial pneumonia, 35 subjects were studied. CC chemokine ligand (CCL)2, CCL3 and CCL4 levels were measured in the bronchoalveolar lavage fluid (BALF) of 18 nonsmoker control subjects and 17 patients affected by IPF. CCR5 expression was evaluated in alveolar macrophages and lymphocytes. The BALF levels of all chemokines were significantly increased in IPF: median (range) CCL3 1.6 (1.0-11.1) versus 1.2 (0.0-3.8) pg x mL(-1); CCL4 6.2 (1.3-96.0) versus 3.4 (0.3-6.8) pg x mL(-1); and CCL2 60.1 (16.7-251.3) versus 4.6 (0.5-119.4) pg x mL(-1). CCL2 levels correlated negatively with the carbon monoxide diffusing capacity of the lung (D(L,CO)) and arterial oxygen tension. CCR5 expression was significantly reduced in lymphocytes from IPF compared with controls. The CC chemokines investigated are involved in the inflammatory mechanisms of idiopathic pulmonary fibrosis, and the results are in agreement with the hypothesis of a downregulation of the T-helper 1 immunological response in this disease.     

间质性肺疾病患者血清和支气管肺泡灌洗液中内皮素1活？…

评价内皮素对肺纤维化发生，发展作用的影响。方法利用同位素放射免疫直接测定法，检测１０例肺结节病和８例特发性肺纤维化患外周血和支气管肺泡灌洗液中内皮素１（ＥＴ－１）的活性，并与８名健康非吸烟进行对照。结论ＥＴ－１在肺结节病和ＩＰＦ发病机制中起着重要作用，并可作为疾病活动性判定的一项重要参考指标。     

Different Expression of Endothelin in the Bronchoalveolar Lavage in Patients with Pulmonary Diseases

Endothelin (ET) is a broncho- and vasoconstrictive cytokine, but it also possesses proinflammatory and mitogenic activity. It is suggested to be involved in the pathogenesis of fibrotic lung diseases. We analyzed the concentration of ET 1 in the bronchoalveolar lavage (BAL) fluid in 95 patients with different lung diseases, among them 41 patients with interstitial lung diseases (13 fibrosing alveolitis in systemic sclerosis (FASS), 9 idiopathic pulmonary fibrosis (IFP), 8 sarcoidosis (S), 6 occupational lung disease (OLD), 5 other alveolitidies A), 27 patients with pneumonia, and 8 patients with chronic obstructive pulmonary disease (COPD). A heterogeneous group of 19 patients served as controls. The median ET concentration was 3.3 pg/ml. Significantly higher concentration was found in patients with FASS (5.8 pg/ml), IPF (5.0 pg/ml), and S (5.1 pg/ml) compared with OLD (2.8 pg/ml), A (1.9 pg/ml), COPD (1.5 pg/ml), and the control group (2.5 pg/ml). In pneumonia, the elevated ET concentration (4.1 pg/ml) was accompanied by a high alveolocapillary leakage. When normalized to BAL albumin concentration, only FASS presented with significantly elevated ET/albumin in the BAL compared with the control group (134.5 vs. 56.l pg/mg, p < 0.05). There were no correlations between ET and BAL differential cell count or pulmonary function tests. In current smokers, ET in BALF was significantly higher compared with non- or ex-smokers (3.9 vs. 2.0 pg/ml, p < 0.01), but not so the ET/albumin ratio (65.0 vs. 62.5 pg/mg). In summary, ET in the BAL is differentially expressed in distinct inflammatory and interstitial lung disease. Consistently high concentrations are found in FASS and elevated ET concentration could be discussed in IPF, sarcoidosis, and pneumonia. ET concentration in BAL is influenced by current smoking habits.     

IL-17和IL-6在特发性肺纤维化患者中的表达及意义

目的探讨特发性肺纤维化患者支气管肺泡灌洗液和血清中白细胞介素-17(IL-17)和白细胞介素-6(IL-6)水平的变化及临床意义。方法选择:31例特发性肺纤维化患者(病例组)和14例健康就诊者(对照组)为研究对象,采用ELISA法检测两组组BALF和外周血中IL-17和IL-6的水平,分析病例组患者IL-17和IL-6水平与其肺功能的关系。结果 IPF组患者血清和BALF中IL-6水平为均明显高于对照组水平(P0.01);IPF组患者血清和BALF中IL-17水平均明显高于对照组水平(P0.01);IPF组患者血清和BALF患者的IL-6和IL-17水平与FVC、FEV1、FEV1∕FVC和DLco水平均呈现明显的负相关性(P均0.01)。结论 IL-17和IL-6可能在IPF的发病过程中发挥一定作用,并有可能作为判断IPF病情严重程度的一项指标。     

Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF.

The purpose of this study was to examine the role of interstitial collagenases, members of the family of matrix metalloproteinases, in the development of pulmonary fibrosis. The activity, levels and molecular forms of collagenases (matrix metalloproteinases (MMP)-1, -8 and -13), gelatinase B (MM P-9) and its main endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and sarcoidosis patients with varying degrees of pulmonary parenchymal involvement. Collagenase activity was elevated in IPF and group 3 sarcoidosis patients. A positive correlation between BALF collagenase activity and MMP-8 levels was also observed. Western immunoblotting revealed the presence of two isoforms of MMP-8 in patient samples; an 80 kD form representing latent enzyme from polymorphonuclear neutrophils and a 55 kD form representing the fibroblast-type proform. MMP-9 levels were also elevated in both IPF and group 3 sarcoidosis patients, while TIMP-1 levels remained normal, indicating a shift in the balance between the enzyme and inhibitor, favouring MMP-9. Matrix metalloproteinase-8 is the major contributor to the bronchoalveolar lavage fluid collagenase activity in the airways of patients with idiopathic pulmonary fibrosis and sarcoidosis and may initiate collagen destruction and remodelling leading to the development of pulmonary fibrosis.     

Immunoenzymatic labeling of monoclonal antibodies for surface antigens of T-cells using immune complexes of APAAP in patients with interstitial lung disease]

The use of unlabeled antibody bridging technique with alkaline phosphatase monoclonal anti-alkaline phosphatase (APAAP) complexes makes it possible to solve the problem of short durability of immunofluorescent staining and the problem of nonspecific endogenous enzyme interference of blood cells with immunoperoxidase method. The technique of APAAP allows satisfactorily to demonstrate the cytoplasmic and surface membrane antigens of T-cells both in peripheral blood and bronchoalveolar lavage fluid (BALF). With the technique studied, the subsets of T-lymphocytes simultaneously in both peripheral blood and BALF of 26 patients with interstitial lung disease and of 16 apparently healthy subjects. The results showed: (1) In patients with interstitial pulmonary fibrosis (IPF) CD8 cells in BALF were higher in number than those in peripheral blood and BALF of normal subjects (P < 0.01). It is suggested that abnormalities of T-Lymphocytes might also play a role in the pathogenesis of IPF. (2) CD4 cells in BALF of patients with sarcoidosis were significantly higher in number than those in other groups (P < 0.01). However, CD8 cells in BALF of patients with sarcoidosis were lower in number than those in others (P < 0.01). The higher ratio of CD4/CD8 was found in sarcoidosis patients during active stage. The findings suggested that change of the ratio of CD4/CD8, as an immunoregulatory abnormalities in lung, could be regarded as one of parameters in assessing the activity in patients with sarcoidosis.     

Increased endothelin-1 levels of BAL fluid in patients with pulmonary sarcoidosis

OBJECTIVE AND BACKGROUND: Pulmonary fibrosis in sarcoidosis is a significant cause of morbidity and mortality. Various factors have been intensely studied to define the pathogenesis of lung fibrosis in sarcoidosis. Endothelin (ET) consists of three isoforms and is known for its potent vasoconstrictor properties. ET plays an important role in the fibroproliferative process of interstitial lung diseases. METHODS: To investigate the role of ET in the progression of pulmonary fibrosis in sarcoidosis, ET-1 and ET-3 concentrations were measured in BAL fluid (BALF) in 22 non-smoking patients with sarcoidosis and in control subjects (n = 12). Immunoreactivity of ET-1 was also evaluated in alveolar macrophages (AMs) from sarcoidosis patients. To assess the effects of ET in BALF on fibroblast proliferation, human foetal lung fibroblasts were cultured with sarcoidosis or control BALFs in the presence or absence of the ET-receptor antagonist TAK-044. RESULTS: ET-1 levels in sarcoidosis BALF were significantly higher than those in control, whereas ET-3 levels were not different between sarcoidosis and control. ET-1 levels were correlated with the number of AMs in BALF. ET-1-immunoreactivity was found mainly in AM of sarcoidosis BALF. Sarcoidosis BALF significantly stimulated fibroblast proliferation, compared with control BALF, and the fibroblast proliferation induced by sarcoidosis BALF was inhibited by TAK-044. CONCLUSIONS: Increased levels of ET-1 in AM could enhance fibrogenesis in pulmonary sarcoidosis.     

还原型辅酶Ⅱ氧化酶蛋白亚单位在特发性肺纤维化患者中的表达

目的探讨特发性肺纤维化（IPF）患者支气管肺泡灌洗液（BALF）和外周血中性粒细胞膜蛋白质和还原型辅酶Ⅱ（NADPH）氧化酶蛋白亚单位p47^-PHOX和p67^-PHOX因子磷酸化表达。方法选择15例IPF患者为病例组，7例无器质性肺疾病者为对照组。采用细胞色素C还原法测定外周血中性粒细胞释放超氧阴离子水平，采用免疫细胞化学法和Western免疫印迹法检测BALF和外周血中性粒细胞膜蛋白质和NADPH氧化酶p47^-PHOX和p67^-PHOX因子磷酸化表达。结果BALF中性粒细胞膜蛋白质磷酸化，IPF组平均吸光度值（0．19±0．02）显著高于对照组（0．14±0．01）；IPF组外周血中性粒细胞膜相对分子质量为80000、58000、45000蛋白质的磷酸化表达和p47^-PHOX和p67^-PHOX因子的磷酸化表达（强阳性）均较对照组（弱阳性）显著增强。IPF组中性粒细胞释放超氧阴离子的水平与用力肺活量、第一秒用力呼气容积、动脉血氧分压、一氧化碳弥散量呈显著负相关。结论外周血中性粒细胞释放超氧阴离子水平与肺纤维化程度存在一定关系。NADPH氧化酶p47^-PHOX和p67^-PHOX因子在IPF患者中表达增加。     

Changes in phospholipids in bronchoalveolar lavage fluid of patients with interstitial lung diseases

We analyzed phospholipids of human bronchoalveolar lavage (BAL) fluids from patients with interstitial lung diseases; idiopathic pulmonary fibrosis (IPF), sarcoidosis, and eosinophilic granuloma (EG) and compared them to those of normal subjects. The content of phospholipid/ml of BAL fluid was significantly decreased in IPF. There was a significant decrease in phosphatidylglycerol (PG) and an increase in phosphatidylinositol (PI) in IPF but not in sarcoidosis and EG. Thus, the PG to PI ratio was significantly decreased in IPF. The dipalmitoyl species of phosphatidylcholine (PC) was found to be significantly decreased in IPF and sarcoidosis by molecular species analysis using high performance liquid chromatography. In contrast, the unsaturated species were increased in these diseases. The decrease in dipalmitoyl PC appeared to be a common feature in interstitial lung diseases. The changes in phospholipids in BAL fluids, especially decreases in DPPC and PG to PI ratio in IPF, appear to indicate that damage of alveolar Type II cells and/or of metabolic disturbance in pulmonary surfactant occurs in IPF.