Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of the composition and significance of individual components of the surfactant indicated that besides phospholipids an important role is played also by surfactant proteins. They aid not only the reduction of the surface tension of the lungs (SP-B, SP-C), but serve also in regulation of surfactant secretion (SP-A) and in local defense and immune responses in the lungs (SP-A and SP-D). Impairments of surfactant were discovered not only in RDS, but also in cases of meconium aspiration, congenital diaphragmatic hernia, pneumonia, pulmonary edema, idiopathic fibrosis of the lungs, alveolar proteinosis, pneumothorax, and bronchial asthma. Therapy by means of exogenous surfactant was proved effective in therapy of RDS. Occasional cases of exogenous surfactant therapy in other pulmonary diseases are auspicious, it is necessary, though, to develop and produce a sufficient amount of exogenous surfactant of high quality and at an acceptable price and to find an optimal manner of surfactant administration into the lungs. A significant perspective is anticipated to utilization of intrapulmonary administration of the exogenous surfactant as a carrier of further active substances for local administration into the lungs. (Ref. 36.)
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PMID:[The pulmonary surfactant factor. Current knowledge, research trends and use in clinical practice]. 788 59

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.
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PMID:Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. 854 13

Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfactant. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism. Tumor necrosis factor-alpha (TNF-alpha), a primary mediator of acute lung inflammation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145-2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody. SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment. Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation. SP-A mRNA was not significantly altered after anti-CD3 antibody and was only mildly decreased after TNF-alpha. As previously reported, intercellular adhesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases associated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases.
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PMID:Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung. 896 4

Study of the pulmonary surfactant system has brought important information about its composition, metabolism and functions in the last decades. Besides phospholipids an important role is played by surfactant proteins (SP-A, B, C, D). These proteins aid not only the reduction of the surface tension of the alveoli, but they are involved in regulation of surfactant synthesis, secretion and in local immune defense in the lungs. Impairment of surfactant was found not only in premature newborns (IRDS), but also in cases of meconium aspiration, pneumonia and in other lung diseases in adults. Therapy by stimulation of surfactant synthesis and secretion and by intrapulmonary application of exogenous surfactant was proved effective in therapy of surfactant-deficiencies.
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PMID:[Pulmonary surfactant]. 899 29

Mycoplasma pneumoniae is a leading cause of pneumonia and exacerbates other respiratory diseases in humans. We investigated the potential role of surfactant protein (SP) A in antimycoplasmal defense using alveolar macrophages (AMs) from C57BL/6NCr (C57BL) mice, which are highly resistant to infections of Mycoplasma pulmonis. C57BL AMs, activated with interferon (IFN)-gamma and incubated with SP-A (25 micrograms/ml) at 37 degrees C, produced significant amounts of nitric oxide (.NO; nitrate and nitrite production = 1.1 microM.h-1.10(5) AMs-1) and effected an 83% decrease in mycoplasma colony-forming units (CFUs) by 6 h postinfection. Preincubation of AMs with the inducible nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished .NO production and SP-A-mediated killing of mycoplasmas. No decrease in CFUs was seen when IFN-gamma-activated macrophages were infected with mycoplasmas in the absence of SP-A despite significant .NO production (nitrate and nitrite production = 0.6 microM.h-1.10(5) AMs-1). These results demonstrate that SP-A mediates killing of mycoplasmas by AMs, possibly through an .NO-dependent mechanism.
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PMID:Surfactant protein A mediates mycoplasmacidal activity of alveolar macrophages. 948 13

Surfactant protein (SP)-A is a known opsonin for a variety of pulmonary pathogens. SP-A enhances ingestion of these pathogens by interaction with an SP-A receptor (SP-AR) found on phagocytic cells such as peripheral blood monocytes (PBMC) and alveolar macrophages. Respiratory syncytial virus (RSV) is the most important respiratory pathogen in children. Recent studies have indicated that SP-A levels may be decreased in RSV bronchiolitis and pneumonia. In this study we examined the role of SP-A in uptake of RSV by both PBMC and U937 macrophages, a human macrophage cell line known to express SP-ARs. In addition, we studied the effect of SP-A- mediated uptake of RSV on production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 by these cells because incomplete immunity to recurrent RSV infection has been partially attributed to abnormal cytokine responses by macrophages. SP-A enhanced binding and uptake of fluorescently labeled RSV (RSV-FITC) by PBMC in a dose-dependent manner, with a maximal effect seen with 10 to 15 microg/ml SP-A as measured by both percent fluorescent monocytes and linear mean fluorescence (lmf) of individual cells. SP-A also enhanced uptake of RSV-FITC by U937 macrophages, with a maximal effect seen with 20 microg/ml SP-A as measured by both percent fluorescent monocytes and lmf. With respect to TNF-alpha levels, RSV alone slightly enhanced TNF-alpha production by PBMC and decreased TNF-alpha production by U937 macrophages measured at 12 h after addition of RSV. SP-A-mediated uptake of RSV significantly enhanced TNF-alpha production by PBMC and reversed the RSV-induced depression of TNF-alpha by U937 macrophages. RSV significantly enhanced IL-10 production by both cell types, which was reversed by SP-A-mediated uptake. These findings suggest that SP-A is an important opsonin for RSV and that SP-A-mediated uptake of RSV may alter some of the unusual cytokine responses that are postulated to be involved in incomplete immunity to recurrent infection.
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PMID:Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages. 1106 36

A 67-year-old man was admitted for acute pneumonia on July 20th, 1999. Chest radiographs disclosed dense consolidation in the right lower lung fields. After admission, the pneumonia underwent rapid advance. On the basis of serological findings and cultures of pleural effusion and sputum, the patient was given a diagnosis of acute pneumonia caused by Legionella pneumophila 1 a. He gradually recovered from the pneumonia by means of chemotherapy using EM, RFP, Mino, gammaglobulins and steroids. The serum SP-A, SP-D, and KL-6 peaked on July 23rd, July 30th, and August 12th, respectively.
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PMID:[A case of severe Legionella pneumonia monitored with serum SP-A, SP-D, and KL-6]. 1132 24

We have previously shown an association between growth factor-induced upregulation of surfactant protein (SP)-A and suppression of alveolar inflammation in our murine model of donor T cell-dependent lung dysfunction after bone-marrow transplantation, referred to as idiopathic pneumonia syndrome (IPS). We hypothesized that SP-A protects the lung in vivo from IPS injury by downregulation of alveolar inflammation. Human SP-A (100 microg), purified by n-butanol extraction or preparative isoelectric focusing, was transtracheally instilled on Day 4 after BMT during a time of in vivo donor T-cell activation. At 48 h after treatment, immunohistochemical staining of lung sections showed that SP-A did not alter T cell- dependent cellular infiltration. However, macrophages from SP-A-instilled mice were less injured and spontaneously produced less tumor necrosis factor-alpha than did cells from buffer-instilled mice. Although exogenous SP-A did not significantly alter bronchoalveolar lavage fluid (BALF) high levels of total protein (TP), an inverse correlation between BALF SP-A and TP concentrations (r = -0.65; P = 0.02) was observed in SP-A-treated but not in buffer-instilled mice. The only difference between the effects of the two sources of SP-A was that butanol-extracted SP-A, but not isoelectric focusing-purified SP-A, suppressed the interferon-gamma/nitric oxide pathway. We conclude that SP-A downregulates T cell-dependent alveolar inflammation by multiple pathways leading to decreased IPS injury.
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PMID:Human surfactant protein a suppresses T cell-dependent inflammation and attenuates the manifestations of idiopathic pneumonia syndrome in mice. 1135 Aug 21

Surfactant proteins SP-A and SP-D, members of the collectin family, have been shown to play a significant role in lung host defense. Both proteins selectively bind Pneumocystis carinii (PC) organisms and modulate the interaction of this pathogen with alveolar macrophages. We hypothesized that the expression and distribution of lung collectins SP-A and SP-D is altered by PC lung infection. PC organisms (2 x 10(5)) were inoculated intratracheally into C.B-17 scid/scid mice that do not require steroids for immunosuppression. Four weeks after inoculation, bronchoalveolar lavage (BAL) fluid was fractionated into three fractions-cell pellet, large aggregate (LA), and small aggregate (SA) surfactant-and each fraction was analyzed for the expression of surfactant components. In uninfected mice, the majority of SP-A (62% +/- 10%) was found in association with lipids in the LA fraction, while 55% +/- 14% of SP-D was distributed in the SA fraction. In contrast, both hydrophobic proteins SP-B and SP-C were associated exclusively with LA. PC infection resulted in major changes in the expression of all surfactant components. Total protein content of LA was unchanged by PC infection (115% +/- 18% of control), whereas SA protein content markedly increased (240% +/- 18% of control level, P <.001). In contrast, the phospholipid content of LA was significantly decreased (53% +/- 5% of control level, P <.001), whereas the SA phospholipid content of infected mice was increased (172% +/- 16% of control level, P <.001). By Western blotting, PC pneumonia (PCP) induced a 3-fold increase in the total alveolar SP-D protein that was reflected mainly in increases in SA SP-D (454% +/- 135% of control, P <.05). The total alveolar SP-A protein content was also increased in PCP because of a large increase in SP-A in SA (720% +/- 115% of control, P <.05); SP-A levels in LA were unchanged. The increases in lung collectin expression were selective, because PCP resulted in the down-regulation of both SP-B and SP-C in LA (5% +/- 2% and 13% +/- 2% of control, respectively, P <.001). We conclude that PCP induces marked elevations in alveolar collectin levels because of increased expression and accumulation of SP-A and SP-D protein in SA surfactant.
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PMID:Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. 1138 64

Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.
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PMID:Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis. 1140 29


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