1.Comparison of the effect of ambroxol and dexamethasone on the expression of pulmonary surfactant proteins in the fetal rat lungs.
Xue-ming FU ; Jia-lin YU ; Guan-xin LIU ; Bing DENG
Chinese Journal of Pediatrics 2004;42(6):450-453
<b>OBJECTIVEb>To investigate the effects of maternally administered dexamethasone and ambroxol on the mRNA levels of surfactant proteins (SP-A, SP-B and SP-C) expression in fetal rat lungs at gestational age day 19.
<b>METHODSb>A 19-day fetal rat lung model was employed. In situ hybridization was used to detect the expression of SP-B mRNA in alveolar type II cell, and the levels of SP-A, SP-B and SP-C mRNAs were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
<b>RESULTSb>(1) SP-B mRNA was detected in situ in alveolar type II cells in fetal rat lung of day 19 gestational age; (2) In the late developmental period of fetal rat lungs, alveolar type II cells were also found around bronchus; (3) Comparing to beta-actin mRNA, the relative values of SP-A, SP-B and SP-C mRNAs were 0.81 +/- 0.26, 0.97 +/- 0.20 and 0.88 +/- 0.11 in fetal lung in the control group. The relative values of mRNAs of SP-A, SP-B and SP-C to beta-actin were 1.04 +/- 0.16, 1.28 +/- 0.29, 1.09 +/- 0.25 in fetal lungs of the ambroxol injected rats, and were 1.08 +/- 0.25, 1.23 +/- 0.35, 1.21 +/- 0.25 in fetal lungs of the dexamethasone injected rats, respectively. Both ambroxol and dexamethasone-treated rats had significantly higher mRNA expression of surfactant proteins compared to the control saline injected animals (P < 0.05). (4) There were no significant differences between ambroxol and dexamethasone in the effects of increasing expressions of surfactant protein mRNAs (P > 0.05).
<b>CONCLUSIONb>Antepartum administration of both ambroxol and dexamethasone can significantly increase fetal lung SP-A, SP-B and SP-C mRNAs expression.
Ambroxol ; pharmacology ; Animals ; Dexamethasone ; pharmacology ; Expectorants ; pharmacology ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Glucocorticoids ; pharmacology ; Lung ; drug effects ; embryology ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction
2.Pulmonary surfactant homeostasis associated genetic abnormalities and lung diseases.
Xiaojing JIANG ; Xiuzhu SUN ; Weihua DU ; Haisheng HAO ; Xueming ZHAO ; Dong WANG ; Huabin ZHU ; Yan LIU
Chinese Journal of Medical Genetics 2016;33(4):564-568
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
3.Influence of vasoactive intestinal peptide on expression of pulmonary surfactant associated protein A in lung explants.
Lian LI ; Zi-qiang LUO ; Gan-qiou WU ; Xiu-hong SUN
Chinese Journal of Applied Physiology 2004;20(2):117-120
<b>AIMb>To study the influence of VIP on the expression of SP-A and its intracellular signal transduction pathway.
<b>METHODSb>The influence of VIP on the expression of SP-A was studied by immunohistochemistry and RT-PCR. The intracellular signal transduction pathway was further investigated by using receptor antagonist, protein kinase inhibitor and antisense oligonucleotides.
<b>RESULTSb>(1) VIP(10(-8) mol/L) enhanced SP-A protein expression in alveolar type II cells (ATII) and increased the content of SP-A mRNA in lung tissue. (2) VIP receptor antagonist [D-P-C1-Phe (6)-Leu (17)]-VIP (10(-6) mol/L) could suppress the VIP-induced expression of SP-A protein and SP-A mRNA. (3) c-fos antisense oligonucleotides (9 x 10(-6) mol/L) could inhibit the VIP-induced expression of SP-A protein and SP-A mRNA. (4) Protein kinase C(PKC) inhibitor H7 (10(-5) mol/L) could also depress the V1P-induced SP-A protein and SP-A mRNA.
<b>CONCLUSIONb>VIP can up-regulate the expression of SP-A through its receptor. PKC and c-fos protein play important roles in the intracellular signal transduction pathway through which VIP induces the expression of SP-A.
Animals ; Epithelial Cells ; drug effects ; metabolism ; In Vitro Techniques ; Protein Kinase C ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Pulmonary Alveoli ; cytology ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; Vasoactive Intestinal Peptide ; pharmacology
4.Pulmonary surfactant associated gene variants in mixed ethnic population of Han and Zhuang.
Yu-jun CHEN ; Shao-ke CHEN ; Kelcey DEPASS ; Daniel J WEGNER ; Aaron HAMVAS ; Guang-min NONG ; Ya-zhou WANG ; Xin FAN ; Jing-si LUO
Chinese Journal of Pediatrics 2012;50(11):843-846
<b>OBJECTIVEb>To explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population.
<b>METHODb>Using a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency.
<b>RESULTb>(1) Altogether, 128 variants were found, including 44 synonymous variants, 66 nonsynonymous variants and 18 insertions-deletions. Of these, 28 variants were predicted to alter protein function. Two of these variants were seen twice, the rest variants were only seen once, for a total of 30 functional alleles; (2) ABCA3 had the most functional variants in both male and female groups with the minor allele frequencies of 0.014 (1.4%) and 0.04 (4%), respectively. The total functional allele frequencies of 6 genes were 0.041 (4.1%) and 0.08 (8%) in the two groups, respectively (P = 0.06).
<b>CONCLUSIONb>(1) Functional variants in pulmonary surfactant associated pathway genes are present in the mixed Han-Zhuang population. (2) ABCA3 contained the most functional variants suggesting that ABCA3 could contribute significantly to neonatal respiratory distress syndrome and other lung disease.
1-Acylglycerophosphocholine O-Acyltransferase ; genetics ; metabolism ; ATP-Binding Cassette Transporters ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; Respiratory Distress Syndrome, Newborn ; ethnology ; genetics
5.Levels of surfactant proteins A and D in bronchoalveolar lavage fluid of children with pneumonia and their relationships with clinical characteristics.
Li-Li WANG ; Shou-Yan ZHENG ; Luo REN ; Qiu-Yan XIAO ; Xiao-Ru LONG ; Jian LUO ; Qu-Bei LI ; Yu DENG ; Xiao-Hong XIE ; En-Mei LIU
Chinese Journal of Contemporary Pediatrics 2016;18(5):386-390
<b>OBJECTIVEb>To observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.
<b>METHODSb>Thirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.
<b>RESULTSb>In children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.
<b>CONCLUSIONSb>SP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.
Bronchoalveolar Lavage Fluid ; chemistry ; C-Reactive Protein ; analysis ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Infant ; Male ; Pneumonia ; metabolism ; Pulmonary Surfactant-Associated Protein A ; analysis ; Pulmonary Surfactant-Associated Protein D ; analysis
6.Expression of HoxB5, SPC and AQP5 in neonatal rats with hyperoxia-induced chronic lung disease.
Wei XU ; Jian-Hua FU ; Xin-Dong XUE
Chinese Journal of Contemporary Pediatrics 2009;11(1):51-55
<b>OBJECTIVEb>Alveolar epithelium impairment is one of pathological changes associated with chronic lung disease (CLD). Hoxb5 is one of the few homeobox genes strongly expressed in the developing lung. This study investigated the expression of HoxB5, SPC and AQP5 in rats with CLD in order to explore the role of Hoxb-5 in impairment and reparation of alveolar epithelium.
<b>METHODSb>Eighty neonatal rats were randomly exposed to hyperoxia (model group) or to room air (control group) (n=40 each). The CLD model was induced by hyperoxia exposure. The expression of HoxB5, SPC and AQP5 protein and mRNA in the lung tissue was detected by immunohistochemistry and RT-PCR 1, 3, 7, 14 and 21 days after exposure.
<b>RESULTSb>In the model group HoxB5 expression significantly decreased 7, 14 and 21 days after hyperoxia exposure. SPC expression decreased 3 days after hyperoxia exposure but increased significantly 7, 14 and 21 days after hyperoxia exposure as compared to the control group. AQP5 expression was progressively reduced with prolonged hyperoxia exposure.
<b>CONCLUSIONSb>Hyperoxia exposure may lead to alveolar epithelial cell (AEC) damage in neonatal rats. The increased SPC expression and decreased AQP5 expression suggested that the ability of differentiation and transformation of AECII into AECI decreased in neonatal rats with CLD. The decreased HoxB5 expression following hyperoxia exposure might contribute to a decreased ability of differentiation of AECII.
Animals ; Animals, Newborn ; Aquaporin 5 ; analysis ; genetics ; Chronic Disease ; Female ; Homeodomain Proteins ; analysis ; genetics ; Hyperoxia ; complications ; Immunohistochemistry ; Lung ; pathology ; Lung Diseases ; etiology ; metabolism ; Male ; Pulmonary Surfactant-Associated Protein C ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction
7.Evaluation and management of inherited disorders of surfactant metabolism.
Chinese Medical Journal 2010;123(20):2943-2947
<b>OBJECTIVEb>To review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).
<b>DATA SOURCESb>Review of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.
<b>STUDY SELECTIONb>Key articles in the field, author's work.
<b>RESULTSb>Inherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,
<b>CONCLUSIONSb>Inherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.
ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism
8.Clinical significance of nuclear factor erythroid 2-related factor 2 in patients with chronic obstructive pulmonary disease.
Woo Ho BAN ; Hyeon Hui KANG ; In Kyoung KIM ; Jick Hwan HA ; Hyonsoo JOO ; Jong Min LEE ; Jeong Uk LIM ; Sang Haak LEE ; Chin Kook RHEE
The Korean Journal of Internal Medicine 2018;33(4):745-752
BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.
Biomarkers
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C-Reactive Protein
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Forced Expiratory Volume
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Humans
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Inflammation
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Interleukin-6
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Korea
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Lung Diseases
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NF-E2-Related Factor 2
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Plasma
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Pulmonary Disease, Chronic Obstructive*
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Pulmonary Surfactant-Associated Protein D
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Respiratory Function Tests
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Vital Capacity
9.Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG.
Maria V CARROLL ; Robert B SIM ; Fabiana BIGI ; Anne JÄKEL ; Robin ANTROBUS ; Daniel A MITCHELL
Protein & Cell 2010;1(9):859-870
Dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN; CD209) has an important role in mediating adherence of Mycobacteria species, including M. tuberculosis and M. bovis BCG to human dendritic cells and macrophages, in which these bacteria can survive intracellularly. DC-SIGN is a C-type lectin, and interactions with mycobacterial cells are believed to occur via mannosylated structures on the mycobacterial surface. Recent studies suggest more varied modes of binding to multiple mycobacterial ligands. Here we identify, by affinity chromatography and mass-spectrometry, four novel ligands of M. bovis BCG that bind to DC-SIGN. The novel ligands are chaperone protein DnaK, 60 kDa chaperonin-1 (Cpn60.1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH) and lipoprotein lprG. Other published work strongly suggests that these are on the cell surface. Of these ligands, lprG appears to bind DC-SIGN via typical proteinglycan interactions, but DnaK and Cpn60.1 binding do not show evidence of carbohydrate-dependent interactions. LprG was also identified as a ligand for DC-SIGNR (L-SIGN; CD299) and the M. tuberculosis orthologue of lprG has been found previously to interact with human toll-like receptor 2. Collectively, these findings offer new targets for combating mycobacterial adhesion and within-host survival, and reinforce the role of DCSIGN as an important host ligand in mycobacterial infection.
Amino Acid Sequence
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Bacterial Adhesion
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physiology
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Bacterial Proteins
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genetics
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metabolism
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Cell Adhesion Molecules
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genetics
;
metabolism
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Chromatography, Affinity
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Dendritic Cells
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metabolism
;
microbiology
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Host-Pathogen Interactions
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genetics
;
physiology
;
Humans
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In Vitro Techniques
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Lectins, C-Type
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genetics
;
metabolism
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Ligands
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Macrophages
;
metabolism
;
microbiology
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Mass Spectrometry
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Membrane Proteins
;
genetics
;
metabolism
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Models, Biological
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Molecular Chaperones
;
genetics
;
metabolism
;
Molecular Sequence Data
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Mycobacterium bovis
;
genetics
;
metabolism
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Mycobacterium tuberculosis
;
genetics
;
metabolism
;
pathogenicity
;
Pulmonary Surfactant-Associated Protein A
;
metabolism
;
Receptors, Cell Surface
;
genetics
;
metabolism
10.Inflammatory reaction and alterations of pulmonary surfactant in Pseudomonas Aeruginosa pneumonia in immunocompromised rats.
Jieming QU ; Zhuozhe LI ; Lixian HE ; Bo SUN ; Xuehua CHEN
Chinese Medical Journal 2002;115(7):1099-1100
Pulmonary surfactant ( PS ) compromises lipids and surfactant proteins (SP) and lines on the alveolar air-liquid interface. It can reduce surface tension, prevent alveoli from collapse and reduce alveoli edema by disaturated dipalmitoylphosphatidylcholine. It also modulates the pulmonary immunology by SP-A and SP-D. In this study,we established a rat model of immunocompromised host (ICH) with pulmonary infection of Pseudomonas aeruginosa (P. aeruginosa), then studied its pulmonary inflammatory reaction and analyzed the concentration of lipids and SP-A in bronchoalveolar lavage fluid (BALF) during infection.
Animals
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Bronchoalveolar Lavage Fluid
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chemistry
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microbiology
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Lipids
;
analysis
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Lung
;
microbiology
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Male
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Neutrophils
;
physiology
;
Pneumonia, Bacterial
;
immunology
;
metabolism
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Proteolipids
;
analysis
;
Pseudomonas Infections
;
immunology
;
metabolism
;
Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Proteins
;
Pulmonary Surfactants
;
analysis
;
Rats
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Rats, Sprague-Dawley