Bronchoalveolar Lavage Fluid Fractions Research Articles

Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells.

Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.

Regulation of Macrophage Foam Cell Formation During Nitrogen Mustard (NM)-Induced Pulmonary Fibrosis by Lung Lipids.

Nitrogen mustard (NM) is a vesicant known to target the lung, causing acute injury which progresses to fibrosis. Evidence suggests that activated macrophages contribute to the pathologic response to NM. In these studies, we analyzed the role of lung lipids generated following NM exposure on macrophage activation and phenotype. Treatment of rats with NM (0.125 mg/kg, i.t.) resulted in a time-related increase in enlarged vacuolated macrophages in the lung. At 28 days postexposure, macrophages stained positively for Oil Red O, a marker of neutral lipids. This was correlated with an accumulation of oxidized phospholipids in lung macrophages and epithelial cells and increases in bronchoalveolar lavage fluid (BAL) phospholipids and cholesterol. RNA-sequencing and immunohistochemical analysis revealed that lipid handling pathways under the control of the transcription factors liver-X receptor (LXR), farnesoid-X receptor (FXR), peroxisome proliferator-activated receptor (PPAR)-ɣ, and sterol regulatory element-binding protein (SREBP) were significantly altered following NM exposure. Whereas at 1-3 days post NM, FXR and the downstream oxidized low-density lipoprotein receptor, Cd36, were increased, Lxr and the lipid efflux transporters, Abca1 and Abcg1, were reduced. Treatment of naïve lung macrophages with phospholipid and cholesterol enriched large aggregate fractions of BAL prepared 3 days after NM exposure resulted in upregulation of Nos2 and Ptgs2, markers of proinflammatory activation, whereas large aggregate fractions prepared 28 days post NM upregulated expression of the anti-inflammatory markers, Il10, Cd163, and Cx3cr1, and induced the formation of lipid-laden foamy macrophages. These data suggest that NM-induced alterations in lipid handling and metabolism drive macrophage foam cell formation, potentially contributing to the development of pulmonary fibrosis.

Identification of Bronchoalveolar Lavage Components Applying Confocal Laser Endomicroscopy.

BackgroundIn many studies, confocal laser endomicroscopy (CLE) has proven to be a useful tool in pulmonology; nevertheless, the application in this field is still experimental. By contrast, CLE is almost a standard technique in gastroenterology. The aim of the present study was to demonstrate the identification of bronchoalveolar lavage (BAL) components applying CLE, using a dye.Material/MethodsIn 21 patients with various underlying diseases a bronchoscopy with BAL was performed. As in routine clinical practice common, BAL fluid (BALF) was analyzed in terms of cytologic, virologic, and microbiologic aspects. To one fraction of BALF, we added acriflavine. After centrifugation CLE was applied and the video sequences were analyzed by an experienced investigator.ResultsUsing CLE, BALF components (such as alveolar macrophages or leucocytes) could be easily identified. A further subdivision of leucocytes (neutrophilic, eosinophilic granulocytes, and lymphocytes) was not possible. Analogous to conventional cytology, a precise distinction of lymphocyte subpopulation (cd 4/cd 8 ratio) was not feasible. In terms of quantification, this is still the application field of flow cytometry and immunohistochemistry.ConclusionsUsing CLE, alveolar macrophages and leucocytes in stained BALF can be differentiated independent of smoking status. Further studies should be initiated in order to subclassify leucocytes in eosinophilic, neutrophilic granulocytes, and lymphocytes, which is important for routine clinical practice.

Cholesteryl esters are elevated in the lipid fraction of bronchoalveolar lavage fluid collected from pediatric cystic fibrosis patients.

BackgroundHost-derived lipids including cholesteryl esters (CEs) such as cholesteryl linoleate have emerged as important antibacterial effectors of innate immunity in the airways and cholesteryl linoleate has been found elevated in the context of inflammation. Cystic fibrosis (CF) patients suffer from chronic infection and severe inflammation in the airways. Here, we identified and quantified CEs in bronchoalveolar lavage fluid (BALF) from CF patients and non-CF disease controls, and tested whether CE concentrations are linked to the disease.Materials and MethodsCEs in BALF from 6 pediatric subjects with CF and 7 pediatric subjects with non-CF chronic lung disease were quantified by mass spectral analysis using liquid chromatography coupled with tandem mass spectrometry and multiple reaction monitoring. BALFs were also examined for total lipid, total protein, albumin, and, as a marker for inflammation, human neutrophil peptide (HNP) 1–3 concentrations. Statistical analysis was conducted after log 10 transformation of the data.ResultsTotal lipid/protein ratio was reduced in CF BALF (p = 0.018) but the concentrations of CEs, including cholesteryl linoleate, were elevated in the total lipid fraction in CF BALF compared to non-CF disease controls (p < 0.050). In addition, the concentrations of CEs and HNP1-3 correlated with one another (p < 0.050).ConclusionsThe data suggests that the lipid composition of BALF is altered in CF with less total lipid relative to protein but with increased CE concentrations in the lipid fraction, likely contributed by inflammation. Future longitudinal studies may reveal the suitability of CEs as a novel biomarker for CF disease activity which may provide new information on the lipid mediated pathophysiology of the disease.

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Eosinophil accumulation is a characteristic feature of the immune response to parasitic worms and allergens. The cell surface carbohydrate-binding receptor Siglec-F is highly expressed on eosinophils and negatively regulates their accumulation during inflammation. Although endogenous ligands for Siglec-F have yet to be biochemically defined, binding studies using glycan arrays have implicated galactose 6-O-sulfate (Gal6S) as a partial recognition determinant for this receptor. Only two sulfotransferases are known to generate Gal6S, namely keratan sulfate galactose 6-O-sulfotransferase (KSGal6ST) and chondroitin 6-O-sulfotransferase 1 (C6ST-1). Here we use mice deficient in both KSGal6ST and C6ST-1 to determine whether these sulfotransferases are required for the generation of endogenous Siglec-F ligands. First, we characterize ligand expression on leukocyte populations and find that ligands are predominantly expressed on cell types also expressing Siglec-F, namely eosinophils, neutrophils, and alveolar macrophages. We also detect Siglec-F ligand activity in bronchoalveolar lavage fluid fractions containing polymeric secreted mucins, including MUC5B. Consistent with these observations, ligands in the lung increase dramatically during infection with the parasitic nematode, Nippostrongylus brasiliensis, which is known to induce eosinophil accumulation and mucus production. Surprisingly, Gal6S is undetectable in sialylated glycans from eosinophils and BAL fluid analyzed by mass spectrometry. Furthermore, none of the ligands we describe are diminished in mice lacking KSGal6ST and C6ST-1, indicating that neither of the known galactose 6-O-sulfotransferases is required for ligand synthesis. These results establish that ligands for Siglec-F are present on several cell types that are relevant during allergic lung inflammation and argue against the widely held view that Gal6S is critical for glycan recognition by this receptor.

Pulmonary pharmacokinetics and safety of nebulized duramycin in healthy male volunteers

Duramycin (Moli1901) is being developed for the treatment of reduced mucociliary clearance in cystic fibrosis. This study was conducted to estimate lung residence time and systemic exposure and to assess whether duramycin causes an inflammatory response. Six volunteers were administered a single dose (7.5 mg) of nebulized duramycin and underwent bronchoscopies to obtain a composite data set for pharmacokinetic analysis; duramycin was measured in the cellular fraction of bronchoalveolar lavage fluid (BALF) (mainly alveolar macrophages) and brush biopsies (bronchial epithelial cells). The estimated t(1/2) of duramycin was approximately 5 days in brush biopsies and 25 to 91 days in BALF cells. Levels of duramycin in BALF (C (max) 800 ng/mg) exceeded those in brush biopsies by approximately 20-fold. Duramycin was absent from plasma and did not cause any detectable inflammatory response in pulmonary tissue as judged from the BALF profile of 14 relevant cytokines. Our data suggest that duramycin qualifies for intrapulmonary administration in cystic fibrosis (CF) patients.

Alterations in Lung Surfactant Disaturated Phosphatidylcholine, SP-A, and SP-B in Meconium Injured Rats Lavaged with Perfluorochemical (PFC) or KL4 Surfactant † 1600

Meconium aspiration remains a common cause of respiratory distress from lung injury and surfactant inhibition. Meconium debris in the lung can be removed by lavage with KL4 surfactant, a mixture of phospholipids (PL) and synthetic peptide (Revak, Pediatr Res, 41;264A,1997), or with PFC which are used to maintain gas exchange. In these models, however the status of lung surfactant composition remains unclear. In a rat model of meconium injury, we have evaluated if lung lavage alters the surfactant disaturated phosphatidylcholine (DSPC) and proteins SP-A and SP-B in spontaneously breathing animals. Adult rats were intubated and given 0.3 ml meconium (13.5 mg dry wt) or saline (NS, n=3) endotracheally. Ten minutes later, meconium instilled lungs (Mec) were lavaged (x 3) with 6 ml/kg aliquots of saline (NSL, n=5) or PFC (PFCL, n=5). One group of Mec rats was lavaged twice with saline suspension of KL4 at 2.5 mg/ml, and once at 10 mg/ml (KL4L, n=5); another group was lavaged twice with saline, followed by once with KL4 at 10mg/ml, in order to replenish surfactant washed out with saline lavages (SKL4L, n=5). Animals were extubated after recovering from anesthesia (1-2 hours) to spontaneously breathe room air for 18 hours, a period previously shown to correlate with maximal lung injury in this model. Thereafter, bronchoalveolar lavage fluid (BAL) was obtained on excised lungs and seperated into large(Lag) and small surfactant aggregates. BAL fractions and lung tissue were analyzed for DSPC content and Lag for SP-A and SP-B. DSPC levels (μg lipid phosphorus/lung) were similar in Lag of Mec (12.5±2.1, mean±SE, n=4) and NS animals (9.5±0.2, p=0.06). They were slightly elevated in PFCL group (14.0±0.5, p>0.05, vs Mec) and significantly elevated in KL4L (87±19, p<0.001, vs Mec) and NSKL4L groups (48±8, p<0.001, vs Mec). DSPC levels in the lung tissue were similar in Mec(138±14) and NS animals 189±17, p=0.06). The lungs of KL4L(330±85, p<0.02) and NSKL4L animals (256±42, p<0.05) also showed higher levels of DSPC compared to Mec animals (138±20). In Western blots of Lag, both SP-A and SP-B were decreased in NSL group compared with NS or Mec animals, suggesting that saline lavage depleted SP. Both proteins were elevated in KL4L compared to NSL animals. We speculate that KL4 lavage may lead to metabolic changes that result in increased retention of PL in lung tissue, and may affect SP metabolism to prevent their depletion in lung surfactant. KL4 was a gift of Acute Therapeutics, Inc, Doylestown, Pa.

Does Early Posttreatment with Lidocaine Attenuate Endotoxin-induced Acute Lung Injury in Rabbits?

It is well known that endotoxin causes acute lung injury, resulting in adult respiratory distress syndrome. Lidocaine pretreatment has recently been shown to attenuate endotoxin-induced lung injury in rabbits. The aim of the current study was to determine whether early postinjury treatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits. Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline (group S-S), infusion of saline with lidocaine treatment (group S-L), infusion of Escherichia coli endotoxin (100 micrograms.kg-1 over a 60-min period) without lidocaine treatment (group E-S), or infusion of endotoxin with lidocaine treatment (group E-L). Ten minutes after the end of infusion of endotoxin (groups E-L and E-S) or saline (groups S-S and S-L), the animals received a bolus injection followed by continuous infusion of lidocaine (2 mg.kg-1 + 2 mg.kg-1.h-1 in groups S-L and E-L) or saline (groups S-S and E-S). The rabbits' lungs were ventilated with 40% O2. Hemodynamics, peripheral leukocyte and platelet counts, and arterial O2 tension (PaO2) were recorded during the ventilation period (6 h). After the observation, lung mechanics; the cell fraction of bronchoalveolar lavage fluid (BALF); and concentrations of activated complement components C3a and C5a, cytokines, and arachidonic acid metabolites in BALF were measured and analyzed. The ratio of lung wet weight to dry weight (W/D weight ratio) and albumin concentrations in BALF were analyzed as indexes of pulmonary edema. The Cypridina luciferin analogue-dependent chemiluminescence (representing O2 production) by neutrophils isolated from the pulmonary artery and light-microscopic findings of the lung were compared among the four groups. Endotoxin caused decreases in peripheral leukocyte and platelet counts, lung compliance, and PaO2. It caused increases in lung W/D weight ratio; polymorphonuclear cell counts in BALF; and albumin, C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and thromboxane B2 concentrations in BALF. Lidocaine attenuated the changes in W/D weight ratio and morphologic lung damage. The change in compliance, decrease in PaO2, and albumin concentrations in BALF were slightly but significantly less in rabbits receiving lidocaine after injury. The Cypridina luciferin analogue-dependent chemiluminescence by neutrophils was greater in rabbits receiving endotoxin without lidocaine than in those receiving endotoxin with lidocaine. These results indicate that early treatment with lidocaine attenuates endotoxin-induced lung edema in rabbits without affecting chemical mediators in BALF. However, the improvement is slight and likely to be of little clinical significance.

Response to airway phagocytes to lung damage before and after strenuous physical exercise

Quantitative ratios between alveolar polymorphonuclear leukocytes (PML) and macrophages and the ingesting and reducing potentials of these phagocytic cells were studied after lung damage in unstressed mice and mice that had just been stressed by strenuous physical exercise (swimming for 60 min). Three days after the lung damage induced in unstressed mice by AgNO3 (0.1 ml instilled intratracheally), PML numbers in the airway lumens were significantly increased, while the bronchoalveolar lavage fluid samples taken on day 14 after lung damage indicated intensified macrophage activity. In the mice instilled with AgNO3 immediately after being stressed, the recruitment of PML and macrophages to the lungs was markedly decreased, although the percentage of macrophages reducing nitro blue tetrazolium had significantly increased. That the lungs of stressed mice sustained less injury than those of unstressed animals was indicated by the finding that lactate dehydrogenase activity in the cell-free fraction of bronchoalveolar lavage fluid was less damaged in response to intratracheal instillation of the destructive agent.

Attenuation of hyperoxic lung injury in rabbits with superoxide dismutase: effects on inflammatory mediators

Superoxide dismutase (SOD) has been shown to attenuate hyperoxic lung injury. This effect is thought to be exhibited by scavenging superoxide released from neutrophils and other aerobic cells. The aim of the current study was to investigate the effect of pre-treatment with SOD on the chemical mediators in hyperoxic lung injury. Thirty male anesthetized rabbits were allocated to receive one of three treatments (n = 10 for each group): ventilated with 100% oxygen for 36 h with or without recombinant human SOD (rhSOD) treatment, and ventilated with air for 36 h without rhSOD. In the rhSOD-treated group, a single intravenous dose of rhSOD 10,000 U kg BW-1 was administered immediately after the start of exposure to 100% oxygen and thereafter infused at a rate of 340,000 U kg BW-1 day-1 for 36 h until the animals were sacrificed. The lungs of all rabbits were ventilated with 100% oxygen or air. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure to 100% oxygen, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolite concentrations in BALF were measured and analyzed. The lung wet-to-dry (W/D) weight ratio and albumin concentrations in BALF were determined as indices of pulmonary oedema. Exposure to the high concentration of oxygen for 36 h caused no significant changes in haemodynamics but decreased compliance and increased A-aDo2. In the rhSOD-treated group, the decrease in compliance was not observed. At the end of the 36 hr-exposure period, however, hyperoxia significantly increased the lung W/D weight ratio, influx of neutrophils into the lung, BALF concentrations of C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, thromboxane B2, and albumin. Pre-treatment with rhSOD attenuated these increases. Exposure to 100% oxygen caused extensive morphologic lung damage (alveolar haemorrhage and hyaline membrane formation), which was lessened by rhSOD. These results indicate that intravenous rhSOD prevented hyperoxic lung injury (decreases in PaO2 and compliance, increased pulmonary vascular permeability, histopathological damage) in rabbits. This prophylactic effect of rhSOD amy be due, in part, to decreased chemical mediators such as activated complements, cytokines, and arachidonic acid metabolites.

Effect of lidocaine pretreatment on endotoxin-induced lung injury in rabbits.

It is well known that endotoxin causes acute lung injury resulting in adult respiratory distress syndrome. Numerous cellular and humoral factors such as macrophages, neutrophils, platelets, and inflammatory mediators (e.g., activated complements, cytokines, and arachidonic acid metabolites) are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury. Furthermore, pulmonary edema in acute lung injury is associated with an increase in vascular permeability that may arise from a perturbation of the endothelial cell surface membrane. Lidocaine has been shown to inhibit function of these cells and stabilize cell membranes. The aim of the current study was to determine whether pretreatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits. Twenty-seven anesthetized male rabbits were randomly assigned to receive one of three treatments (n = 9 for each group); infusion of saline (as a control), infusion of Escherichia coli endotoxin (30 micrograms kg-1 over a 60-min period) without treatment with lidocaine, and infusion of endotoxin with treatment with lidocaine. A single dose of intravenous lidocaine 2 mg.kg-1 was administered 10 min before infusion of endotoxin and thereafter infused at a rate of 2 mg.kg-1.h-1 until 6 h after the start of endotoxin administration, when the animals were killed. The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocytes counts, and arterial oxygen tension were recorded during the ventilation period. After the observation, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolites concentrations in BALF were measured and analyzed. The lung wet-to-dry-weight ratio and albumin concentrations in BALF were analyzed as an indices of pulmonary edema. The cypridina luciferin analog-dependent chemiluminescence (representing superoxide production) by neutrophils isolated from the pulmonary artery and light microscopic findings were compared among the three groups. Endotoxin caused decreases in peripheral leukocyte counts, lung compliance, and arterial oxygen tension, and increases in the lung wet-to dry-weight ratio, polymorphonuclear cell counts in BALF, and albumin, C3a, C5a, tumor necrosis factor alpha, interleukin-1 beta, and thromboxane B2 concentrations in BALF. Lidocaine pretreatment attenuated these changes. The cypridina luciferin analog--dependent chemiluminescence was greater in rabbits receiving endotoxin than in the control. Lidocaine pretreatment attenuated the increase in chemiluminescence. Endotoxin caused extensive morphologic lung damage, which was lessened by lidocaine. These results suggest that intravenous lidocaine pretreatment has a prophylactic effect on endotoxin-induced lung injury in rabbits. However, further studies are required to investigate the therapeutic (as an early posttreatment) effect of the drug given after lung injury because rabbits in the current study received lidocaine before endotoxemia.

Cardiopulmonary bypass significantly reduces surfactant activity in children

Lung injury remains an important problem after cardiopulmonary bypass. The contribution of altered surfactant concentration or activity to pulmonary dysfunction after cardiopulmonary bypass is unclear. Recent evidence indicates that alveolar surfactant exists in specific aggregate forms that differ with respect to density, phospholipid composition, and function. A transition from surface active, higher density, large aggregates of surfactant to lower density, small aggregates that possess reduced surface activity has been demonstrated after experimental lung injury. The purpose of the present study was to examine surfactant aggregate fractions before and after bypass in children. Twelve acyanotic patients, aged 2 to 12 years, underwent intraoperative pulmonary function testing followed by bronchoalveolar lavage before incision and approximately 1 hour after termination of cardiopulmonary bypass. Saturated phosphatidylcholine pool sizes and total protein content of the small- and large-aggregate fractions of bronchoalveolar lavage fluid were determined. One hour after termination of cardiopulmonary bypass, the ratio of saturated phosphatidylcholine in small-aggregate as compared with that in large-aggregate fractions increased (mean +/- standard error) from 0.19 +/- 0.03 to 0.37 +/- 0.07 (p < 0.02), as did the ratio of saturated phosphatidylcholine to protein in the small-aggregate fraction (from 0.04 +/- 0.01 to 0.08 +/- 0.02, p < 0.05). Reductions in forced vital capacity (-19% +/- 5%), inspiratory capacity (-15% +/- 3%), and small airway flow rates (-32% +/- 6%) were also observed after bypass. These changes were accompanied by a fivefold increase in alveolar polymorphonuclear leukocyte content. The present study suggests that cardiopulmonary bypass of moderate duration in relatively healthy children is associated with surfactant changes that are similar in type and magnitude to those observed in experimental lung injury.

Pulmonary Corpora Amylacea Contain Surfactant Apoprotein

The case of a 53-year-old female with interstitial pneumonitis is described with special regard to biochemical characterization of pulmonary corpora amylacea which were found in the lung specimen obtained by bronchial biopsy from the patient. The main protein component in bronchoalveolar lavage (BAL) fluid of the patient was albumin, but proteins in the precipitate fraction of BAL fluid, where the corpora amylacea were recovered, predominantly consisted of 36 kD protein which was stained with the monoclonal antibody PE 10 to human pulmonary surfactant apoprotein by immunoblot. Histologically the pulmonary corpora amylacea were stained with eosin and PAS. The particles were stained immunohistochemically by immunoperoxidase reaction using PE 10, but not by antibodies to human albumin. The pulmonary surfactant apoprotein seems, therefore, to be not simply adsorbed in the particles, but to be contained in them. Thus, the surfactant apoprotein may, at least in this case, be involved in the formation of pulmonary corpora amylacea.

Changes in Surfactant in Bronchoalveolar Lavage Fluid after Hemithorax Irradiation in Patients with Mesothelioma

Experimental studies have shown that the surfactant system of the lung is affected shortly after irradiation. It is unclear, however, whether surfactant plays a role in the pathogenesis of radiation pneumonitis. In the present study surfactant components (saturated phosphatidylcholine, surfactant protein A, phosphatidylglycerol, and phosphatidylinositol) and other phospholipids of bronchoalveolar lavage fluid (BAL) were studied in four patients with pleural mesothelioma before and during hemithorax irradiation (70 Gy) as well as zero, 1, 2, 3, and 4 months following irradiation. The concentrations of these same components and of soluble proteins were also estimated in the epithelial lining fluid (ELF) using urea as a marker of dilution. After radiotherapy, the concentrations of the surfactant components in ELF decreased to 12 to 55% of the control values before radiation, whereas the concentration of sphingomyelin in ELF increased ninefold. There were small changes in the other phospholipids. The concentration of soluble protein in ELF increased sevenfold. The minimum surface activity of crude BAL increased from 12 +/- 4 to 32 +/- 6 mN/m, and that of the sediment fraction of BAL increased from 7 +/- 4 to 22 +/- 6 mN/m, p less than 0.001. The protein-rich supernatant fraction of BAL from irradiated lung had a inhibitory effect on normal surfactant. There were significant correlations between the increasing severity of the radiologic changes on the one hand and, on the other, the saturated phosphatidylcholine/sphingomyelin ratio (p less than 0.001), the concentrations of soluble protein (p less than 0.001), and the concentrations of the surfactant components (p less than 0.02-0.001) in ELF.(ABSTRACT TRUNCATED AT 250 WORDS)

気管支ぜん息症例における気管支肺胞洗浄液中のアラキドン酸代謝産物

Contributions of prostaglandin (PG) s, thromboxane (TX) s, and leukotriene (LT) s in the pathophysiology of bronchial asthma have not been clarified yet. In the experimental model of bronchial asthma, SRS-A and histamine are known to play an important role. But clinical analysis is rare. In this investigation we performed broncho-alveolar lavage (BAL) in bronchial asthma patients and measured chemical mediators in three fractions of BAL fluid (BALF) and peripheral venous blood.TXB2 and 11-dehydro-TXB2 were significantly increased in the BALF of patients with bronchial asthma. But their concentrations in the peripheral venous blood are not so high compared with those of control groups. PGD2 and PGF2α were not detected in the peripheral venous blood, but their levels in BALF were elevated in BALF of patient with bronchial asthma. Levels of leukotriene C4 were not elevated in BALF and peripheral venous blood compared with those of control group, but further study would be needed to evaluate the role of leukotrienes including LTC4 and LTD4.

Plasminogen activator in bronchoalveolar fluid.

Plasminogen activator was purified from the soluble fraction of bronchoalveolar lavage fluid, and biological and immunological characteristics of the activator were examined by electrophoretic enzymography. The purified fraction showed a single band with a molecular weight of 53,000. The enzyme activity was eliminated in the presence of DFP and did not display fibrin affinity. Immunological tests revealed that the plasminogen activator reacted with IgG of antiurokinase but not with that of tissue-type plasminogen activator. However, the plasminogen activator cleaved S-2288 to a greater extent than S-2444 in contrast to urokinase.

Changes in fatty acids in phospholipids of the bronchoalveolar fluid in bacterial pneumonia and in adult respiratory distress syndrome.

Fatty acids of the phospholipid fraction of bronchoalveolar lavage fluid from patients with bacterial pneumonia or with the adult respiratory distress syndrome were chromatographed and the patterns compared with those for a control group. In the control group, palmitic acid (16:0) was the predominant fatty acid, accounting for 58.0% (SD 8.25%) of the total fatty acid, a proportion significantly higher (p less than 0.001) than in the distress-syndrome group (42.1%, SD 4.88%) or the acute pneumonia group (32.1%, SD 1.73%). There was a greater proportion of oleic acid (18:1) in the disease groups; thus the ratio of palmitic to oleic acid was useful in distinguishing these three groups. No patient with a palmitic/oleic acid ratio greater than 2.45 had evidence of parenchymal inflammation. Of those with a ratio less than 1.3, 89% had acute bacterial pneumonia.