The pathophysiology of meconium aspiration syndrome(MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. Meconium is also suggested to cause functional deterioration of pulmonary surfactant. Recent studies have reported that meconium inhibits the physical surface properties of pulmonary surfactant, and that administration of exogenous surfactant may provide therapeutic benefits in animal models or infants with respiratory distress due to MAS. To assess the effects of meconium on physical surface properties, especially the changes on the air-liquid interface and hypophase of pulmonary surfactant in vitro, we studied the following findings; a) the surface spreading rate(SSR) and the surface adsorption rate(SAR), b) the viscosity, c) the electron microscopic changes, on a series of mixtures with various concentrations of lyophilized human meconium and Surfactant-TA(SurfactenTM). The human meconium has significantly increased the surface tension of SSR and the viscosity of pulmonary surfactant, but had decreased the surface pressure of SAR of surfactant, and changed the electron microscopic findings of surfactant. We have concluded that these findings support the concept that meconium-induced surfactant dysfunction may play a role in the pathophysiology of MAS.
Human ; Infant, Newborn ; Meconium/*metabolism ; Pulmonary Surfactants/*metabolism

OBJECTIVETo investigate the relationship between the recovery levels of pulmonary surfactants (PS) and lung compliance after whole-lung lavage.

METHODSPatients with pneumoconiosis in different stages (healthy subjects, stage I, and stage II, n = 10 for each group) were selected. The recovery levels of PS and lung compliance at different time points after whole-lung lavage were determined, and their relationship was analyzed.

RESULTSBefore whole-lung lavage and at 0, 10, 30, 60, 90, and 120 min after the operation, the lung compliance levels were 39.5±6.7, 28.3±5.6, 31.5±5.2, 37.6±4.4, 38.0±5.3, 38.7±5.5, and 39.2±5.3 ml/cm H2O for healthy subjects, 38.8±5.1, 25.1±6.1, 28.4±6.8, 30.5±5.9, 36.3±5.5, 37.3±5.4, 38.2±4.5, and 38.8±5.1 ml/cm H2O for patients with stage I pneumoconiosis, and 32.9±6.1, 20.3±6.0, 24.3±5.4, 25.1±5.4, 26.8±5.8, 27.8±4.8, and 32.8±4.5 ml/cm H2O were for patients with stage II pneumoconiosis. It was observed that in patients with pneumoconiosis, the lung compliance levels showed a declining trend along with the increasing stage, reaching the lowest level in stage II patients; comparison between groups indicated a significant difference (P < 0.05). For healthy subjects, 30 min was needed for restoring lung compliance to its preoperative level, while 60 and 120 min were needed for stage I and stage II patients, respectively. Compared with that at 0 min after operation, PS levels were elevated significantly at 10 min after operation in all patients (P < 0.05), whereas for stage I and stage II patients, the PS levels at 30 min after operation were significantly higher than that at 10 min (F = 4.27, P < 0.05; F = 20.40, P < 0.05). For all patients, the PS levels at 60 min after operation were significantly higher than those at 10 and 30 min (P < 0.05). After whole-lung lavage, the PS levels in all patients were restored to a large extent within 10∼30 min, but the recovery of lung compliance needed 30∼ 90 min.

CONCLUSIONAfter whole-lung lavage, the lung compliance declines obviously, but recovers gradually afterwards; the higher stage suggests a longer recovery. The recovery of lung compliance needs a longer time than that of PS.

Adult ; Bronchoalveolar Lavage ; Humans ; Lung Compliance ; Male ; Middle Aged ; Pneumoconiosis ; metabolism ; physiopathology ; therapy ; Pulmonary Surfactants

OBJECTIVETo investigate the protective and therapeutic effects of pulmonary surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in hamsters.

METHODSCOPD animal model was established by smoke inhalations and intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters were divided into 9 groups as follows: normal group (N), two groups received smoke inhalations for 1 and 3 months (S1 and S3), one group received intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months of smoking (SP3), and two groups received intratracheal administration of elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0, 1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3). EP1 group were killed at the first month, and EP3 at the third month. Light microscopy and electromicroscopy observations were performed in each group. Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured by image analysis. The expression of surfactant protein A (SP-A) were observed by immunohistochemistry.

RESULTSSmoking for 3 months and instillations of elastase resulted in chronic bronchitis and emphysema. MLI and PAA increased and MAN decreased in all the experimental groups compared with in the normal group (P < 0.05 or P < 0.01). Administration of surfactant for 3 months resulted in statistically significant inhibition of pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the type II alveolar epithelia decreased in S3 and E3 (compared with the normal group P < 0.01). After pulmonary surfactant intervention, the expression of SP-A increased significantly.

CONCLUSIONPulmonary surfactant may have a long-term protective effect on chronic smoking and elastase-induced COPD.

Animals ; Cricetinae ; Male ; Mesocricetus ; Pancreatic Elastase ; Pulmonary Alveoli ; ultrastructure ; Pulmonary Disease, Chronic Obstructive ; metabolism ; prevention & control ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Pulmonary Surfactants ; therapeutic use ; Smoking

OBJECTIVETo observe the changes of pulmonary surfactant (PS) in rats with acute lung injury(ALI) induced by lipopolysaccharide (LPS) and to explore the effects of hydrogen sulfide (H2S) on PS.

METHODSFourty- eight male rats were randomly divided into six groups (n = 8). They were control group, LPS group, LPS+ NaHS low, middle, high dose groups and LPS+ PPG group. Saline was administrated in Control group. LPS was administrated in LPS group. In LPS + NaHS low, middle, high dose groups or LPS + PPG group, sodium hydrosulfide (NaHS) of different doses or DL-propargylglycine (PPG) were respectively administrated when the rats were administrated of LPS after 3 hours. All the rats were killed at 6 hours after administration of Saline or LPS. The morphological changes of alveolar epithelial type II cells (AEC-II) were respectively observed by transmission electron microscopes. The content of H2S in plasma and activity of cystathionine-gamma-lyase (CSE) in lung tissues were respectively detected. The contents of total protein (TP) and total phospholipids (TPL) in bronchoalveolar lavage fluid (BLAF) were respectively measured. The pulmonary surfactant protein A (SP-A), surfactant protein B (SP-B) and surfactant protein-C (SP-C) mRNA expressions in lung tissues were analysed.

RESULTS(1) Compared with control group, the content of H2S in plasma, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased in LPS group (P < 0.05 or P < 0.01). But the content of TP was increased in LPS group (P < 0.01); (2) Compared with LPS group, the content of H2S, activity of CSE and SP-A mRNA expression were significantly increased in LPS + NaHS low, middle and high dose groups (P < 0.05). The SP-B mRNA expression and content of TPL were significantly increased in LPS + NaHS Middle and High dose groups (P < 0.05). The content of TP was decreased in LPS + NaHS High dose group (P < 0.05). The SP-C mRNA expression was not altered in LPS+ NaHS low, middle and high dose groups (P > 0.05); (3) Compared with LPS group, the content of H2S, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased, but content of TP was increased in LPS + PPG group (P < 0.05).

CONCUSIONThe decrease of PS is the important physiopathologic process of ALI induced by LPS. Exogenously applied H2S could attenuate the process of ALI that possibly because H2S could adjust the compose and secretion of PS.

Acute Lung Injury ; chemically induced ; metabolism ; Animals ; Hydrogen Sulfide ; metabolism ; pharmacology ; Lipopolysaccharides ; Male ; Pulmonary Surfactants ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the change of the subfractions in existence (big and small polymers) of pulmonary surfactant (PS) and their influence on the decrease in PS activity during early postburn stage.

METHODSForty rabbits were employed in the study and were randomly divided into pre-burn, 0.5 postburn hour (PBH), 2 PBH, 6 PBH and 12 PBH groups with 8 in each group. The BALF (bronchial alveolar lavage fluid) was harvested from each rabbit. The BALF samples were centrifuged, and the supernatant (small polymer) and precipitation (big polymer) were harvested for the determination of the contents of the total phospholipids, lecithin, total protein, and albumin in both polymers.

RESULTSCompared with those in pre-burn group, the above chemical contents of PS in big polymer exhibited no change after burn (P > 0.05), but the contents of albumin and total protein increased obviously in small polymer (P < 0.01). In addition, all the contents in the small polymer increased with the elapse of time. The percentage of lecithin in total phospholipids in small polymers decreased along with the passage of time. The pre-burn contents of total phospholipids, lecithin, TP, albumin, and the percentage of lecithin in total phospholipid in small polymer were (2.23 +/- 0.40),(1.54 +/- 0.11), (16.67 +/- 1.34), (3.65 +/- 0.15) mg/ml and (77.2 +/- 3.7)%, respectively. The above indices in small polymer were (3.15 +/- 0.30), (1.77 +/- 0.08), (106.59 +/- 5.50), (11.21 +/- 0.92) mg/ml and (57.2 +/- 3.5)% respectively at 6PBH.

CONCLUSIONThe ratio of small to big polymers increased obviously, which might be an important factor in inducing the decrease in PS activity during early postburn stage leading finally to pulmonary injury.

Albumins ; analysis ; Animals ; Female ; Male ; Phosphatidylcholines ; analysis ; Phospholipids ; analysis ; Pulmonary Surfactants ; metabolism ; Rabbits ; Smoke Inhalation Injury ; metabolism

OBJECTIVETo study the changes to surfactant proteins in the serum and bronchoalveolar lavage fluids (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and their significance.

METHODSSelf-control method was used in the study. Forty-seven MPP children were divided into single lung infected (n=32) and bilateral lung infected groups (n=15) according to lung CT results. Surfactant proteins SP-A, B, C and D were measured using ELISA in the serum and BALF in the two groups. The correlations between SP-A, B, C and D content in the serum and BALF were evaluated by Spearman correlation analysis.

RESULTSSP-A, B, C and D content in BALF from the majorly infected or infected lung were significantly higher than from the opposite lung and serum (P<0.01). SP-A, B and C content in serum was significantly lower than in BALF from the non-infected lung in the single-side infected lung group (P<0.01 or 0.05), but there was no significant difference between serum SP-D content and BALF SP-D content from the non-infected lung. There were no significant differences in SP-A, B, C and D content in serum and BALF from the minorly infected lung in the bilateral lung infected group. Serum SP-D content was positively correlated with BALF SP-D content from the majorly infected lung in the bilateral lung infected group (P<0.01).

CONCLUSIONSSerum SP-D content may serve as a biomarker for evaluating the severity of pulmonary infection in children with community-acquired pneumonia.

Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Pneumonia, Mycoplasma ; metabolism ; Pulmonary Surfactants ; analysis ; blood

OBJECTIVETo investigate the effects of methylprednisolone pretreatment on pulmonary lung permeability index and the content of the pulmonary surfactant dipalmitoylphosphatidylcholine (DPPC) in a rabbit model of reexpansion pulmonary edema.

METHODSTwenty-one male New Zealand white rabbits were randomly divided into control group, reexpansion, and reexpansion+methylprednisolone pretreatment groups. The rabbit model of reexpansion pulmonary edema was established using Sakaos method. A bolus dosage of methylprednisolone (3 mg/kg) in reexpansion+methylprednisolone group group or 2.0 ml/kg normal saline in the other two groups was administered intravenously 20 min before reexpansion pulmonary edema. Bronchoalveolar lavage fluid (BALF) and arterial blood samples were collected for measurement of the total protein (TP) and DPPC contents 4 h after reexpansion, and the pulmonary permeability index was calculated.

RESULTSThe pulmonary permeability index in methylprednisolone pretreatment group was significantly lower than that in the reexpansion group (0.007∓0.002 vs 0.177∓0.004, P<0.05). Methylprednisolone pretreatment significantly increased DPPC concentration in the BALF as compared with saline treatment in the reexpansion group (61.815∓28.307 vs 101.955∓24.544 µg/ml, P<0.05).

CONCLUSIONMethylprednisolone pretreatment can increase pulmonary surfactant content and improve pulmonary permeability in the rabbit model of reexpansion pulmonary edema.

1,2-Dipalmitoylphosphatidylcholine ; analysis ; Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; drug effects ; Male ; Methylprednisolone ; pharmacology ; Permeability ; Pulmonary Edema ; metabolism ; physiopathology ; Pulmonary Surfactants ; metabolism ; Rabbits

Adaptation, Physiological ; Animals ; Biological Transport ; Epithelial Sodium Channels ; physiology ; Extravascular Lung Water ; metabolism ; Fetus ; metabolism ; Humans ; Infant, Newborn ; Lung ; metabolism ; Pulmonary Surfactants ; metabolism

Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
ATP-Binding Cassette Transporters ; genetics ; DNA-Binding Proteins ; genetics ; Homeostasis ; Humans ; Lung Diseases ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism ; Transcription Factors

OBJECTIVETo investigate the effect of L-Arginine (L-Arg) on pulmonary surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary injury induced by lipopolysaccharide (LPS).

METHODSModel of acute lung injury (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was administrated at 3 h or 6 h after LPS injection respectively for 3 h. The expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD rats and harvested by selective plating technique. LPS and L-Arg were added to the culture medium. The concentration of nitric oxide (NO),the activity of lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively measured.

RESULTSCompared with the control group, the expression of SP-A mRNA was significantly decreased, the TP concentration was significantly increased in LPS group. Compared with LPS group at the same time points, treatment with L-Arg at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased markedly, whereas TP concentration was decreased significantly. In cultured rat AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were significantly increased in LPS group to compared with those of control group. LDH activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with those of LPS group.

CONCLUSIONL-Arg can protect the lung against LPS-induced pulmonary injury by up-regulating the expression of PS and inhibiting inflammatory transmitters from AM.

Acute Lung Injury ; chemically induced ; drug therapy ; metabolism ; Animals ; Arginine ; pharmacology ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Macrophages, Alveolar ; metabolism ; Male ; Pulmonary Surfactants ; metabolism ; Rats ; Rats, Sprague-Dawley