Does serum angiotensin converting enzyme reflect intensity of alveolitis in sarcoidosis?

Serum angiotensin converting enzyme activity is increased in many patients with pulmonary sarcoidosis and has been proposed as a measure of disease activity. Assay of serum angiotensin converting enzyme, bronchoalveolar lavage, and gallium scans were performed in 27 patients with biopsy proved pulmonary sarcoidosis. There was a positive correlation between serum angiotensin converting enzyme activity and an index of pulmonary gallium uptake assessed by the National Institutes of Health method (r = 0.7, p less than 0.001). There was no significant relationship (r = 0.19) between serum angiotensin converting enzyme activity and bronchoalveolar lavage lymphocytes expressed as a proportion of cells recovered. Increase in the enzyme activity had a sensitivity of 50% as a means of detecting high intensity alveolitis but specificity was only 45%. There was no significant difference in mean angiotensin converting enzyme activity between the following groups: those with positive and those with negative gallium scans; those with bronchoalveolar lavage lymphocyte counts less than or equal to 28% and those with counts greater than 28%. Although there was a significant correlation between the enzyme activity and one component of the alveolitis of sarcoidosis, the data suggest that serum angiotensin converting enzyme activity alone is neither sensitive nor specific enough for high intensity alveolitis.     

Collagenase and fibronectin in bronchoalveolar lavage fluid in patients with sarcoidosis

Bronchoalveolar lavage fluid from 43 patients with biopsy proved sarcoidosis and 10 control subjects were assayed for fibronectin and collagenase activity. Fibronectin was significantly increased in the group with sarcoidosis and was found to be positively correlated with angiotensin converting enzyme activity, protein concentration, percentage of T cells and helper:suppressor ratios in the lavage fluid. Increased fibronectin in the bronchoalveolar lavage fluid was not related to functional or radiographic indices of interstitial disease and did not identify patients subsequently requiring treatment. Latent collagenase was present in bronchoalveolar lavage fluid from 16 patients with sarcoidosis but not in any control sample. There was no association between the collagenase activity and the cell profiles of the lavage fluid. Yet carbon monoxide transfer factor was decreased in patients with bronchoalveolar lavage fluid collagenase. Ten of 16 patients with bronchoalveolar lavage fluid collagenase had radiographic class III or IV disease and a disease duration of more than two years. On follow up 62% of patients with bronchoalveolar lavage fluid collagenase required subsequent treatment, compared with only 23% of patients without collagenase. These results indicate an association between bronchoalveolar lavage fluid collagenase and progressive, prolonged disease in sarcoidosis, whereas increased bronchoalveolar lavage fluid fibronectin is associated with indices of disease activity.     

Effect of monocrotaline ingestion on the distribution of protein and angiotensin converting enzyme activity in the rat lung.

The alveolar accumulation of protein and angiotensin converting enzyme activity was compared with the development of right ventricular hypertrophy in male rats after different periods of monocrotaline exposure. Total doses of monocrotaline were varied by dividing the animals into three groups in which ingestion was limited to three, seven, and 15 days. These groups were studied 21 days after the start of monocrotaline exposure and compared with a group treated continuously for 28 days. The total lung weight increased after three or more days of treatment, while after seven days there was significant alveolar accumulation of protein, which was paralleled by an increase in angiotensin converting enzyme activity in alveolar lavage fluid. Identical changes also occurred after 15 and 28 days of exposure to monocrotaline. Lung angiotensin converting enzyme activity was decreased after three days' ingestion of monocrotaline and did not alter further with longer periods of exposure. None of these effects of monocrotaline in the three and seven day treatment groups was associated with right ventricular hypertrophy, which occurred only in animals treated for 15 or more days. The effects of monocrotaline ingestion on the lung were dose related and had no causal relationship to the development of right ventricular hypertrophy.     

Collagen breakdown during acute lung injury.

Injury to the capillary endothelium and to alveolar epithelial cells of the lung may result in damage to the underlying collagen of the extracellular matrix. To examine this possibility, whole body irradiation, bleomycin injections, and exposure to hyperoxia were used to induce various types of lung damage in mice. The morphology of the lung and the cellular and protein content of bronchoalveolar lavage fluid were used to assess injury. Collagen breakdown was assessed from the hydroxyproline concentrations in bronchoalveolar lavage fluid. When lung cell injury was observed, protein leaked in to alveoli and hydroxyproline was detected in bronchoalveolar lavage fluid. An increase in hydroxyproline followed endothelial damage by irradiation and was greatly increased when type 1 epithelial cell necrosis also occurred after bleomycin injection or hyperoxia. Maximal concentrations of hydroxyproline occurred in mice showing respiratory distress after six days of hyperoxia. Concentrations returned to zero during the subsequent phases of cell regeneration and fibrosis seen after bleomycin injection and irradiation. There was little change in the cellular components of bronchoalveolar lavage fluid at any time. The results indicate that collagen breakdown occurs during acute lung injury and can be quantified in terms of the hydroxyproline concentration in lavage fluid. Such a change in the extracellular matrix might influence the subsequent division and differentiation of regenerating cells during repair.     

Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of alveolar macrophages in controls, indicating that it may come from these cells. LACE was high in active sarcoidosis while in inactive disease it was similar to that in controls. SACE in sarcoidosis was significantly increased. Ninety per cent of patients with increased L albumin had increased SACE. SACE activity was significantly correlated with concentrations of L albumin and with LACE activity. The relationships between signs of increased membrane permeability and SACE and between LACE and SACE suggest that excess SACE in sarcoidosis may, at least partly, originate in the alveolar space.     

蒸汽吸入性损伤犬支气管肺泡灌洗液的观察

为了探讨吸入性损伤后支气管肺泡灌洗液检测的意义,选用12条本地健康杂种犬进行自身对照试验。采用蒸汽致伤造成重度吸入性损伤,在伤后1小时和5小时观察支气管肺泡灌洗液(BALF)中细胞成份、总蛋白含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和血管紧张素转换酶(ACE)活性的变化。结果表明,吸入性损伤后肺内大量炎性细胞渗出,脂质过氧化反应水平增高和肺毛细血管内皮细胞损伤。     

Relation between immunocytological features of bronchoalveolar lavage fluid and clinical indices in sarcoidosis.

This study was designed to determine whether cell populations in bronchoalveolar lavage fluid represent a reflection of disease activity in sarcoidosis. Bronchoalveolar lavage fluid cells were obtained from 22 patients with sarcoidosis and from 10 normal control subjects and investigated by immunocytological methods. A panel of monoclonal antibodies was used to determine the relative proportions of phenotypically distinct subsets of macrophages and lymphocytes in the patients with sarcoidosis and to correlate them with clinical indices, such as disease duration, serum angiotensin converting enzyme, the chest radiograph, and results of pulmonary function tests. Patients with sarcoidosis had a higher percentage than the normal subjects of macrophage like cells expressing RFD1 (a class II associated antigen preferentially expressed by dendritic cells), an epithelioid cell antigen (RFD9), and a circulating monocyte antigen (UCHMI). The increase in RFD1+ cells appeared to be due to detection of antigen by this antibody on cells that were also expressing phenotypic markers of classical tissue macrophages (RFD7). The lymphocytes in lavage fluid from patients with sarcoidosis were characterised by increased expression of activation markers, such as interleukin-2 receptors (anti-Tac+), HLA-DR (RFDR+), and "blast" forms (expressing above normal concentrations of CD7 antigen). This was associated with increased proportions of the CD4+ (helper-inducer) T cell subset. Patients with sarcoidosis whose clinical indices suggested activity showed an increased number of macrophages coexpressing RFD1 and RFD7 antigens, of macrophages expressing UCHM1 and lymphocytes expressing activation markers. The expression of these markers was also increased on lavage cells from patients with radiographic evidence of widespread disease (chest radiographic stage II and III), but there was no relation with disease duration, pulmonary function, or serum angiotensin converting enzyme activity. Immunocytological analysis of lavage cells offers a probe for studying the pathogenesis of sarcoidosis and may be of value in monitoring disease activity.     

蒸汽吸入性损伤犬支气管肺泡灌洗液的观察

为了探讨吸入性损伤后支气管肺泡灌洗液检测的意义，选用１２条本地健康杂种犬进行自身对照试验。采用蒸汽致伤造成重度吸入性损伤，在伤后１小时和５小时观察支气管肺泡灌洗液（ＢＡＬＦ）中细胞成份、总蛋白含量、丙二醛（ＭＤＡ）含量、超氧化物歧化酶（ＳＯＤ）活性和血管紧张素转换酶（ＡＣＥ）活性的变化。结果表明，吸入性损伤后肺内大量炎性细胞渗出，脂质过氧化反应水平增高和肺毛细血管内皮细胞损伤     

Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model

BACKGROUND: Injurious mechanical ventilation can cause a pro-inflammatory reaction in the lungs. Recent evidence suggests an association of the renin-angiotensin system (RAS) with lung inflammation. A study was undertaken to investigate the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and to determine whether VILI can be attenuated by angiotensin converting enzyme (ACE) inhibition. METHODS: Male Sprague-Dawley rats were mechanically ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non-ventilated rats were used as controls. Lung injury and inflammation were measured by the lung injury score, protein leakage, myeloperoxidase activity, pro-inflammatory cytokine levels and nuclear factor (NF)-kappaB activity. Expression of the RAS components was also assessed. Some rats were pretreated with the ACE inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during mechanical ventilation to assess possible protective effects on VILI. RESULTS: In the high-volume group (n=6) the lung injury score, bronchoalveolar lavage fluid protein concentration, pro-inflammatory cytokines and NF-kappaB activities were significantly increased compared with controls (n=6). Lung tissue angiotensin II levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II receptors were also significantly increased in the high-volume group. Pretreatment with captopril or concomitant infusion with losartan or PD123319 in the high-volume group attenuated the lung injury and inflammation (n=6 for each group). CONCLUSIONS: The RAS is involved in the pathogenesis of ventilator-induced lung injury. ACE inhibitor or angiotensin receptor antagonists can attenuate VILI in this rat model.     

七氟醚对内毒素致急性肺损伤鼠肺泡毛细血管膜通透性的影响

目的　探讨七氟醚对内毒素致急性肺损伤鼠肺泡毛细血管膜通透性和肺泡灌洗液内炎性细胞的影响。方法　 4 8只Wistar大鼠 ,麻醉后静注伊万斯蓝 5 0mg/kg后 ,随机分为 4组 ,每组 12只。对照组 :股静脉注射生理盐水 1 2ml后机械通气 4h ;内毒素组 :股静脉注射内毒素 5mg/kg后机械通气 4h ;七氟醚 1L组和七氟醚 2L组 :股静脉注射内毒素 5mg/kg后机械通气 ,分别吸入肺泡气最低有效浓度 (MAC)为 1 0和 1 5的七氟醚 4h。 4h后取肺组织测定 :病理形态学积分 ,肺湿 /干重比 ,肺水含量 ,肺通透指数 ,伊万斯蓝含量和肺泡灌洗液内炎性细胞总数及百分比。结果　七氟醚1L组肺通透指数、伊万斯蓝含量、病理形态学积分分别由 4 6 8± 0 82 ,( 112 2 1± 11 4 4 )ng/mg ,9 17± 0 90下降到 3 98± 0 5 0 ,( 92 85± 11 80 )ng/mg ,7 5 0± 0 96 ;七氟醚 2L组下降到 3 91±0 34,( 96 33± 8 79)ng/mg ,7 6 7± 0 75。结论　 1 0和 1 5MAC七氟醚可降低内毒素所致急性肺损伤肺泡毛细血管膜通透性 ,使肺组织病理损伤减轻     

Role of polymorphonuclear leukocytes in experimental lung injury--chemotaxis and active oxygen metabolite production

To clarify the role of polymorphonuclear leucocytes (PMNs) in acute lung injury, acute experimental lung injury was produced by intravenous injection of endotoxin to male Hartley guinea pigs. White blood cell (WBC) counts in the peripheral blood, total nucleated cell counts and PMNs' population in the lung lavage fluid, chemotaxis and chemiluminescence of the PMNs in the blood and in the lung lavage fluid were studied. Results were as following 1. WBC counts in the blood decreased after injection of endotoxin. In the lung lavage fluid, total nucleated cell counts and the differential counts of PMNs increased with time. 2. The chemotaxis of PMNs in the blood decreased significantly (647 +/- 118 cells/5 high-power-fields (5HPF) in no treatment group (NT group), vs 256 +/- 120 cells/5HPF in 6 hours after endotoxin injection group (6h group), p less than 0.01), but that in the lung lavage fluid increased significantly (93 +/- 63 cells/5HPF in NT group, vs 334 +/- 24 cells/5HPF in 6h group p less than 0.01). 3. The chemiluminescence of the PMNs in the blood increased (3.64 +/- 2.41 counts/cell in NT group, vs 51.2 +/- 32.9 counts/cell in 6h group, p less than 0.01), and that in the lung lavage fluid increased (1.89 +/- 0.94 counts/cell NT group, vs 59.2 +/- 49.1 counts/cell in 6h group, p less than 0.01). We concluded that increased chemotaxis of PMNs contributed to the influx of PMNs into the alveolar spaces after endotoxin injection. As the pMNs in the alveolar spaces had increased ability to produce active oxygen metabolite, they might be involved in the progression of endotoxin-induced acute lung injury.     

Endothelial selectin blockade attenuates lung permeability of experimental acid aspiration

BACKGROUND: A central role for the polymorphonuclear leukocyte (PMN) in experimental acid aspiration has been demonstrated by the observation that PMN depletion reduced pulmonary vascular permeability. This study investigates the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating acid aspiration lung injury. METHODS: Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of (125)I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed. RESULTS: PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 1 mg/kg rPSGL-Ig before acid aspiration. PMN count of 19 +/- 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 +/- 72. The respective PI in mice treated with rPSGL-Ig (1/2) hour and 1 hour after acid aspiration was 45% and 39% reduced compared with the untreated group. CONCLUSIONS: Endothelial selectin blockade is as effective as PMN depletion in moderating acid aspiration induced lung permeability. Delayed antiselectin therapy can decrease lung injury.     

Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests.

To study the relationship between the results of bronchoalveolar lavage and pulmonary function tests during induction and progression of asbestosis, three groups of six sheep were exposed repeatedly by intratracheal injection to either saline (controls), low doses of Canadian chrysotile UICC asbestos (cumulative exposure 328 mg) (low-dose group), or high doses of the same fibres (cumulative dose 2282 mg) (high-dose group) until there was clear evidence of alveolitis from the lung biopsy specimens of all sheep of the high-dose group. During the course of this induction and for the following eight months lung biopsies, bronchoalveolar lavage and pulmonary function tests were performed at two-month intervals. At the time of initial alveolitis in the high-dose group there was no significant change in the cellularity of the bronchoalveolar lavage fluid, but static lung compliance (Cst), vital capacity (VC), arterial oxygen tension (Pao2), and diffusion capacity (DL/VA) were significantly lower than in the other groups. In the following months, as the alveolitis evolved into a fibrosing process, macrophages and neutrophils from the bronchoalveolar lavage fluid increased significantly and pulmonary function deteriorated. Proteins and enzymes in the bronchoalveolar lavage fluid also increased significantly in the high-dose group. These data show that in the sheep model of asbestosis simple tests of pulmonary function correlate well with histological changes and changes in the bronchoalveolar lavage fluid in the course of the disease and can be used to assess progression of asbestosis.     

Experimental studies on changes of SOD activity levels and reperfusion injury after lung transplantation

The purpose of this study is to evaluate the role of superoxide dismutase (SOD) in reperfusion injury after lung transplantation in mongrel dogs. Canine left lungs were used and three groups were studied. Group I underwent complete hilar stripping (n = 6). Group II underwent complete hilar stripping and was kept in warm ischemia for 60 min. by clamping left pulmonary artery and veins (n = 6). Group III underwent the same surgery as Group II and kept in warm ischemia for 120 min (n = 6). To evaluate the function of the lung, arterial blood gas, left total pulmonary resistance (ITPR) and lung wet to dry weight ratio (W/D ratio) were measured in transient contralateral pulmonary arterial occlusion periodically for 7 days after reperfusion. Also, plasma and bronchoalveolar lavage fluid (BALF) levels of SOD like activity, angiotensin converting enzyme (ACE) activity and ceruloplasmin were measured before operation and periodically after reventilation and reperfusion. Additionally, using dialyzer and electron spin resonance (ESR) spectrometry, plasma levels of extracellular SOD (EC-SOD) activity were measured. The results obtained were as follows. 1) In Group II and III, W/D ratio, ITPR and arterial blood gas were significantly increased in comparison with Group I. 2) Though there were no significant changes in the BALF levels of SOD like activity, ACE and ceruloplasmin and in the plasma levels of ACE and ceruloplasmin, the plasma level of SOD like activity rose 3 hours after reperfusion. 3) The plasma level of EC-SOD activity rose along with that of SOD like activity without any change in intra-cellular SOD levels. The above results suggest that EC-SOD plays an important role in cyto-protection against reperfusion injury after lung transplantation.     

Rapid diagnosis of gram negative pneumonia by assay of endotoxin in bronchoalveolar lavage fluid.

BACKGROUND: Diagnosis of ventilator associated pneumonia can be made by quantitative cultures of bronchoalveolar lavage fluid or of protected specimen brushings, though cultures require 24-48 hours to provide results. In 80% of cases aerobic Gram negative bacteria are the cause. METHODS: A rapid diagnostic method of assessing the endotoxin content of lavage fluid by Limulus assay is described. Forty samples of lavage fluid were obtained from patients with multiple trauma requiring mechanical ventilation for a prolonged period. Pneumonia was diagnosed on the basis of clinical, radiological, and bacteriological findings, including quantitative cultures of lavage fluid. RESULTS: A relation was observed between the concentration of endotoxin in lavage fluid and the quantity of Gram negative bacteria. The median endotoxin content of lavage fluid in Gram negative bacterial pneumonia was 15 endotoxin units (EU)/ml; the range observed in individual patients was 6 to > 150 EU/ml. In patients with pneumonia due to Gram positive cocci and in non-infected patients the median endotoxin level was 0.17 (range < or = 0.06 to 2) EU/ml. An endotoxin level greater than or equal to 6 EU/ml distinguished patients with Gram negative bacterial pneumonia from colonised patients and from those with pneumonia due to Gram positive cocci. CONCLUSION: The measurement of endotoxin in lavage fluid is a rapid (less than two hours) and accurate diagnostic method. It should allow specific and early treatment of Gram negative bacterial pneumonia.     

Role of inflammation in nocturnal asthma.

BACKGROUND--Nocturnal airway narrowing is a common problem for patients with asthma but the role of inflammation in its pathogenesis is unclear. Overnight changes in airway inflammatory cell populations were studied in patients with nocturnal asthma and in control normal subjects. METHODS--Bronchoscopies were performed at 0400 hours and 1600 hours in eight healthy subjects and in 10 patients with nocturnal asthma (> 15% overnight fall in peak flow plus at least one awakening/week with asthma). The two bronchoscopies were separated by at least five days, and both the order of bronchoscopies and site of bronchoalveolar lavage (middle lobe or lingula with contralateral lower lobe bronchial biopsy) were randomised. RESULTS--In the normal subjects there was no difference in cell numbers and differential cell counts in bronchoalveolar lavage fluid between 0400 and 1600 hours, but in the nocturnal asthmatic subjects both eosinophil counts (median 0.11 x 10(5) cells/ml at 0400 hours, 0.05 x 10(5) cells/ml at 1600 hours) and lymphocyte numbers (0.06 x 10(5) cells/ml at 0400 hours, 0.03 x 10(5) cells/ml at 1600 hours) increased at 0400 hours, along with an increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid (3.0 micrograms/ml at 0400 hours, 2.0 micrograms/l at 1600 hours). There were no changes in cell populations in the bronchial biopsies or in alveolar macrophage production of hydrogen peroxide, GM-CSF, or TNF alpha in either normal or asthmatic subjects at 0400 and 1600 hours. There was no correlation between changes in overnight airway function and changes in cell populations in the bronchoalveolar lavage fluid. CONCLUSIONS--This study confirms that there are increases in inflammatory cell populations in the airway fluid at night in asthmatic but not in normal subjects. The results have also shown a nocturnal increase in eosinophil cationic protein levels in bronchoalveolar lavage fluid, but these findings do not prove that these inflammatory changes cause nocturnal airway narrowing.     

内毒素性肺损伤外周血中性粒细胞CD11b表达的意义

目的：探讨内毒素血症大鼠外周血中性粒细胞（PMN）表面CD11b表达与内毒素性肺损伤的关系。方法：大肠杆菌E-Coli O111B4 4mg／kg尾静脉注射制备大鼠内毒素血症动物模型。112只大鼠随机分为对照组（静脉注射等量生理盐水）及内毒素注射后1h组、2h组、4h组、8h组、12h组、24h组,每组16只动物。在相应时间点放血处死动物,分别取股静脉血、肺组织及进行支气管肺泡灌洗,测定肺组织湿／干重（W／D）比值、肺组织髓过氧化物酶（MPO）活性和支气管肺泡灌洗液（BALF）总蛋白定量等肺损伤指标。流式细胞仪测定外周血PMN表面CD11b表达。另取16只大鼠,内毒素注射后2h时测定外周血PMN表面CD11b表达,24h时放血处死,测定上述指标。结果：①大鼠内毒素血症可以造成明显的急性肺损伤,表现为肺组织W／D比值、MPO活性和BALF总蛋白明显增高,分别在2h、8h和2h显著高于对照组（P〈0．05或P〈0．01）,峰值分别出现在内毒素注射后12h、24h和12h;②大鼠内毒素性肺损伤时,外周血PMN表面CD11b表达水平在早期（1h）明显升高（与对照组比较,P〈O．05）,在2h达到峰值,之后逐渐降低;③外周血CD11b表达峰值明显早于肺组织W／D比、MPO和BALF总蛋白等肺损伤指标的峰值出现时间;④同一动物2h时外周血PMN表面CD11b的表达水平与其24h时肺组织W／D比、MPO和BALF总蛋白含量呈显著正相关（r分别为0．78、0．77和0．73,P〈0．05）。结论：内毒素性肺损伤中,外周血CD11b表达升高可能有助于内毒素性肺损伤的早期诊断,并可能预示以后的肺损伤程度。     

Warm ischemia induces alteration in lung immune cell functions

Warm ischemia is an important factor in early allograft dysfunction. To elucidate cellular events involved in such lung injury, we examined the effects of warm ischemia on the cytotoxic function of lymphocytes retrieved by bronchoalveolar lavage as compared with peripheral blood lymphocytes. Warm ischemia of the lung was induced in eight dogs by crossclamping left hilar structures for 1 hour. Bronchoalveolar cells from ischemia left and unaffected right lungs, as well as blood lymphocytes, were isolated before operation and 2 hours, 72 hours, and 7 days after operation. Lung and blood lymphocytes were assayed for natural killer and lectin-dependent cell-mediated cytotoxicity. Warm ischemia resulted in a significant impairment of natural killer activity within 2 hours of reperfusion (49% of preoperative control cytolysis, p less than 0.01). There was a significant increase in natural killer activity in bronchoalveolar lavage mononuclear cells 72 hours after reperfusion injury (178.4% of preoperative value, p less than 0.01). Interestingly, these functional alterations were not paralleled with changes seen in the peripheral blood lymphocytes or the opposite nonaffected lungs, where the natural killer activity appeared significantly depressed at 72 hours. Similarly, lectin-dependent cell-mediated cytotoxicity was noted to be increased in the bronchoalveolar lavage from the ischemic lung (179.5%, p less than 0.01) but decreased in the bronchoalveolar lavage from the nonaffected lung and peripheral blood lymphocytes at 72 hours after injury. We conclude that warm ischemia is associated with a functional alteration of the local lung immune cells. Such alteration is not observed in cells from the opposite lung or peripheral blood. The observed increase in nonspecific cytotoxicity of bronchoalveolar lymphocytes can be causative in the early damage seen in poorly preserved lung allografts.     

Specification and quantitation of circulating immune complexes in the serum of patients with active pulmonary sarcoidosis.

BACKGROUND--Circulating immune complexes can be elevated in serum samples of patients with sarcoidosis and are associated with disease activity, but their diagnostic significance is not understood. METHODS--The different classes of circulating immune complexes containing immunoglobulin A, G, or M, and the content of complement in circulating immune complexes (polyethylene glycol precipitation) as well as levels of complement binding circulating immune complexes (complement binding assay) were determined in 19 patients with active, untreated pulmonary sarcoidosis. The results were compared with other parameters in the serum (soluble interleukin 2 receptor, angiotensin converting enzyme, immunoglobulin A, G, and M) and the bronchoalveolar lavage fluid (lymphocytes, helper cells, suppressor cells, activated T cells), and with radiological stage and functional parameters (FEV1, vital capacity, total lung capacity, transfer coefficient (KCO), and the alveolar-arterial oxygen difference during exercise). RESULTS--In all patients circulating immune complexes could be detected by polyethylene glycol precipitation and were similar to control subjects. The content of C1q in circulating immune complexes was higher than in controls, yet in all but one of the cases was still within normal limits. In contrast, elevated levels of complement binding circulating immune complexes were found in 67% of the patients. No correlation was seen between circulating immune complexes and any of the other parameters in the serum, bronchoalveolar lavage fluid, or lung function values. No differences were found between radiological type I and II presentations of sarcoidosis. CONCLUSIONS--The complement binding assay showed a much higher sensitivity for the detection of circulating immune complexes in active pulmonary sarcoidosis than the polyethylene glycol precipitation method. As there was no correlation between levels of circulating immune complexes and other parameters of the disease they are probably not useful for the assessment of disease activity.