The Experts below are selected from a list of 4728 Experts worldwide ranked by ideXlab platform

Fred Possmayer - One of the best experts on this subject based on the ideXlab platform.

  • pulmonary Surfactant Protein a sp a restores the surface properties of Surfactant after oxidation by a mechanism that requires the cys6 interchain disulfide bond and the phospholipid binding domain
    Journal of Biological Chemistry, 2003
    Co-Authors: Karina Rodriguez Capote, Francis X Mccormack, Fred Possmayer
    Abstract:

    Abstract Reactive oxygen species produced by activated leuko-cytes in the alveolar epithelial lining fluid have been implicated in the inactivation of pulmonary Surfactant and the impairment of lung function. Oxidation of bovine lipid extract Surfactant (BLES), a therapeutic Surfactant, with hypochlorous acid (H-BLES) or the Fenton reaction (F-BLES) led to temporary increases in conjugated dienes and formation of malondialdehyde and 4-hydroxy-2-nonenal. Electrospray ionization mass spectrometry revealed the appearance of lipid hydroperoxides, peroxides, lysophospholipids, and free fatty acids. Captive bubble tensiometer studies of H-BLES demonstrated prolonged adsorption times, film instability at low surface tensions during film compression, and reduced respreadability during film expansion. F-BLES exhibited prolonged adsorption times, a marked effect on increasing compressibility during compression, and a lesser effect on reducing respreadability on expansion. Addition of native bovine or rat Surfactant-Associated Protein A (SP-A) reversed the effects of oxidation on Surfactant biophysical properties. Studies using mutant recombinant rat SP-As indicated that an intact carbohydrate recognition domain and disulfide-dependent oligomeric assembly are critical for these effects, but the collagen-like region is not required. We conclude that SP-A can reverse the detrimental effects of Surfactant oxidation on the biophysical properties of Surfactant, by a mechanism that is dependent on interchain disulfide bond formation and the C-terminal domains of the Protein.

  • changes in Surfactant Associated Protein mrna profile in growth restricted fetal sheep
    American Journal of Physiology-lung Cellular and Molecular Physiology, 1999
    Co-Authors: Robert Gagnon, Johnathan Langridge, Kevin Inchley, Jun Murotsuki, Fred Possmayer
    Abstract:

    To test the hypothesis that chronic placental insufficiency resulting in fetal growth restriction causes an increase in fetal lung Surfactant-Associated Protein (SP) gene expression, we embolized c...

  • recombinant rat Surfactant Associated Protein d inhibits human t lymphocyte proliferation and il 2 production
    Journal of Immunology, 1998
    Co-Authors: Paul Borron, Fred Possmayer, Jo Rae Wright, James F Lewis, Erika C Crouch, Laurence J Fraher
    Abstract:

    Components of the airspace-lining material may contribute to the local regulation of immune function within the lung. We report here that recombinant rat pulmonary Surfactant-Associated Protein D (SP-D) inhibits the lectin- and anti-CD3-stimulated proliferation of human PBMCs. Inhibition was Associated with a decreased production of IL-2, and the addition of human rIL-2 blocked the inhibitory action of SP-D. These effects were not inhibited by maltose, indicating that the inhibitory activity was not dependent upon the lectin activity of SP-D. Studies employing mutant SP-D lacking N-linked sugars or defective in multimerization further indicated that inhibition was not dependent upon cellular interactions with the N-linked oligosaccharide on SP-D or the oligomerization of trimeric SP-D subunits. Although a peptide containing an inverted DGR showed similar IL-2-dependent effects on anti-CD3-stimulated proliferation, deletion of the conserved DGRDGR sequence near the amino-terminal end of the collagen domain did not decrease the suppressive activity of SP-D. We hypothesize that SP-D can dampen lymphocyte responses to exogenous stimuli and protect the lung against collateral immune-mediated damage.

  • role of the palmitoylation of Surfactant Associated Protein c in Surfactant film formation and stability
    American Journal of Physiology-lung Cellular and Molecular Physiology, 1996
    Co-Authors: R Qanbar, Fred Possmayer, S Cheng, S Schurch
    Abstract:

    The effect of palmitoylation of pulmonary Surfactant-Associated Protein C (SP-C) on the surface activity of phospholipid mixtures of dipalmitoylphosphatidylcholine and phosphatidylglycerol was studied. Phospholipids reconstituted with palmitoylated or depalmitoylated bovine SP-C were examined at neutral and acidic pH using a captive bubble surfactometer. At low pH, effective lipid adsorption and near zero surface tensions upon compression were obtained even with Protein-free samples. At physiological pH, only SP-C-containing samples achieved such properties. Lipid adsorption was decreased by prior SP-C depalmitoylation. Bubbles with palmitoylated SP-C were more mechanically stable and required less compression to reach low surface tensions. Subphase depletion experiments showed that dynamically cycled surface layers containing palmitoylated SP-C maintained their surface activity after subphase lipid depletion. In contrast, surface activity was rapidly lost where depalmitoylated SP-C or SP-B was included. Our results indicate that although SP-C palmitoylation has little effect on its ability to enhance lipid adsorption and surface tension reduction, it greatly enhances lipid respreading and film stability and is therefore important for Surfactant function.

  • Surfactant Associated Protein a inhibits human lymphocyte proliferation and il 2 production
    American Journal of Respiratory Cell and Molecular Biology, 1996
    Co-Authors: Paul Borron, Kevin Inchley, Fred Possmayer, Ruud A W Veldhuizen, James F Lewis, Anita Caveney, R G Mcfadden, Laurence J Fraher
    Abstract:

    The hyporesponsive state of lung-derived mononuclear leukocytes has been, in part, attributed to the effects of the lipid rather than the Protein components of pulmonary Surfactant. In the present study, however, the results suggest that purified preparations of pulmonary Surfactant-Associated Protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 microgram/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferation of human peripheral blood and tonsillar mononuclear cells in a dose-dependent manner at concentrations as low as 50 pM (6.25 micrograms/ml) when added at the initiation of cultures. Addition of SP-A to PHA-stimulated peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h after PHA was also capable of suppressing [3H]thymidine incorporation measured at 72 h. In contrast, concanavalin A (Con A; 2 micrograms/ml)-stimulated PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentrations, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and less than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 micrograms/ml, respectively. We suggest that the action of SP-A on PHA-stimulated human PBMC may involve the blocking of a costimulatory signal crucial for in vitro T-cell activation.

Jeanne M Snyder - One of the best experts on this subject based on the ideXlab platform.

  • Surfactant Associated Protein a provides critical immunoprotection in neonatal mice
    Infection and Immunity, 2008
    Co-Authors: Caroline L S George, Kelli L Goss, David K Meyerholz, Fred S Lamb, Jeanne M Snyder
    Abstract:

    The collectins Surfactant-Associated Protein A (SP-A) and SP-D are components of innate immunity that are present before birth. Both Proteins bind pathogens and assist in clearing infection. The significance of SP-A and SP-D as components of the neonatal immune system has not been investigated. To determine the role of SP-A and SP-D in neonatal immunity, wild-type, SP-A null, and SP-D null mice were bred in a bacterium-laden environment (corn dust bedding) or in a semisterile environment (cellulose fiber bedding). When reared in the corn dust bedding, SP-A null pups had significant mortality (P < 0.001) compared to both wild-type and SP-D null pups exposed to the same environment. The mortality of the SP-A null pups was Associated with significant gastrointestinal tract pathology but little lung pathology. Moribund SP-A null newborn mice exhibited Bacillus sp. and Enterococcus sp. peritonitis. When the mother or newborn produced SP-A, newborn survival was significantly improved (P < 0.05) compared to the results when there was a complete absence of SP-A in both the mother and the pup. Significant sources of SP-A likely to protect a newborn include the neonatal lung and gastrointestinal tract but not the lactating mammary tissue of the mother. Furthermore, exogenous SP-A delivered by mouth to newborn SP-A null pups with SP-A null mothers improved newborn survival in the corn dust environment. Therefore, a lack of SP-D did not affect newborn survival, while SP-A produced by either the mother or the pup or oral exogenous SP-A significantly reduced newborn mortality Associated with environmentally induced infection in SP-A null newborns.

  • Altered Surfactant Protein A gene expression and Protein metabolism Associated with repeat exposure to inhaled endotoxin
    American journal of physiology. Lung cellular and molecular physiology, 2003
    Co-Authors: Caroline L S George, Misty L. White, Marsha E. O'neill, Peter S. Thorne, David A. Schwartz, Jeanne M Snyder
    Abstract:

    Chronically inhaled endotoxin, which is ubiquitous in many occupational and domestic environments, can adversely affect the respiratory system resulting in an inflammatory response and decreased lung function. Surfactant-Associated Protein A (SP-A) is part of the lung innate immune system and may attenuate the inflammatory response in various types of lung injury. Using a murine model to mimic occupational exposures to endotoxin, we hypothesized that SP-A gene expression and Protein would be elevated in response to repeat exposure to inhaled grain dust and to purified lipopolysaccharide (LPS). Our results demonstrate that repeat exposure to inhaled endotoxin, either in the form of grain dust or purified LPS, results in increased whole lung SP-A gene expression and type II alveolar epithelial cell hyperplasia, whereas SP-A Protein levels in lung lavage fluid are decreased. Furthermore, these alterations in SP-A gene activity and Protein metabolism are dependent on an intact endotoxin signaling system.

  • localization of Surfactant Associated Protein c sp c mrna in fetal rabbit lung tissue by in situ hybridization
    American Journal of Respiratory Cell and Molecular Biology, 1992
    Co-Authors: Christine L Wohlfordlenane, Paul L Durham, Jeanne M Snyder
    Abstract:

    .Surfactant is a lipoProtein substance that is synthesized and secreted by alveolar type II epithelial cells and acts to reduce surface tension at the air-alveolar interface. SP-C is a 5,OOO-D molecular weight, hydro­ phobic, Surfactant-Associated Protein. In the present study, we used a ribonuclease protection assay to show that SP-C mRNA is induced in rabbit fetal lung tissue early in development, increases in relative concentration as development proceeds, and is present in maximal concentration at term (31 days of gesta­ tion). We also used the technique of in situ hybridization to localize SP-C mRNA in fetal, neonatal, and adult rabbit lung tissue. SP-C mRNA was present in all of the epithelial cells of the prealveolar region of day 19 gestational age rabbit fetal lung tissue, i.e., about 7 days before the appearance of differentiated alveolar type II cells in the fetal lung tissue. By day 27 of gestation, SP-C mRNA was restricted to epithe­ lial cells with the morphologic characteristics of alveolar type II cells. SP-C mRNA was not detected in bronchiolar epithelium at any stage of lung development. The intensity of SP-C mRNA hybridization in the prealveolar and alveolar type II epithelial cells increased as a function of gestational age and was maxi­ mal at term. The pattern of SP-C mRNA localization in neonatal and adult rabbit lung tissue was consistent with the restriction of SP-C gene expression to differentiated alveolar type II cells. Our data are suggestive that SP-C may serve some as yet unknown function early in lung development because it is present in fetal lung prealveolar epithelial cells much earlier in gestation than are differentiated, Surfactant­ producing alveolar type II cells.

Masayuki Noguchi - One of the best experts on this subject based on the ideXlab platform.

  • phenotypic characteristics of mouse lung adenoma induced by 4 methylnitrosamino 1 3 pyridyl 1 butanone
    Molecular Carcinogenesis, 2005
    Co-Authors: Chigusa Okubo, Yukio Morishita, Yuko Minami, Tadashi Ishiyama, Junko Kano, Tatsuo Iijima, Masayuki Noguchi
    Abstract:

    The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of Surfactant-Associated Protein A (SP-A) and lysozyme showed characteristically higher transcription in the adenoma tissue than in normal lung. High expression of both SP-A and lysozyme in tumor cells was confirmed by in situ hybridization (ISH). In normal lung, alveolar type II pneumocytes were positive for both SP-A and lysozyme, indicating that tumor cells retained the phenotypic characteristics of the murine alveolar type II pneumocytes. Previous studies of human adenocarcinomas have shown that the two Proteins are expressed reciprocally; SP-A and lysozyme are differential markers of atypical adenomatous hyperplasia (AAH) and non-goblet cell type adenocarcinoma, and of goblet cell type adenocarcinoma, respectively. Thus, the present results indicate that the phenotype of NNK-induced A/J mouse adenoma differs from that of AAH, which is thought to be a preinvasive lesion of human adenocarcinoma.

David S Strayer - One of the best experts on this subject based on the ideXlab platform.

  • survival signaling in type ii pneumocytes activated by Surfactant Protein a
    Experimental Cell Research, 2002
    Co-Authors: Martyn K White, David S Strayer
    Abstract:

    Surfactant-Associated Protein-A (SP-A) is a component of pulmonary Surfactant that acts as a cytokine through interaction with a cell-surface receptor (SPAR) on lung epithelial cells. SP-A regulates important physiological processes including Surfactant secretion, gene expression, and protection against apoptosis. Tyrosine kinase and PI3K inhibitors block effects of SP-A, suggesting that SPAR may be a receptor tyrosine kinase and activate the PI3K-PKB/Akt pathway. Here we report that SP-A treatment leads to rapid tyrosine-specific phosphorylation of several important Proteins in lung epithelial cells including insulin receptor substrate-1 (IRS-1), an upstream activator of PI3K. Analysis of anti-apoptotic signaling species downstream of IRS-1 showed activation of PKB/Akt but not of MAPK. Phosphorylation of IkappaB was minimally affected by SP-A as was NFkappaB gel shift activity. However, FKHR was rapidly phosphorylated in response to SP-A and its DNA-binding activity was significantly reduced. Since FKHR is pro-apoptotic, this may play an important role in signaling the anti-apoptotic effects of SP-A. Therefore, we have characterized survival-enhancing signaling activated by SP-A leading from SPAR through IRS-1, PI3K, PKB/Akt, and FKHR. The activity of this pathway may explain, in part, the resilience of type II cells to lung injury and their survival to repopulate alveolar epithelium after peripheral lung damage.

  • natural protection from apoptosis by Surfactant Protein a in type ii pneumocytes
    Experimental Cell Research, 2001
    Co-Authors: Martyn K White, Vijayabhasker Baireddy, David S Strayer
    Abstract:

    Surfactant-Associated Protein A (SP-A) is a component of pulmonary Surfactant that binds to a specific receptor (SPAR) on the surface of type II alveolar cells of the lung and regulates gene expression and Surfactant secretion. Previously we have shown that activation of SPAR by SP-A binding initiates a signal through pathways that involve tyrosine phosphorylation, include IRS-1, and entail activation of phosphatidylinositol 3-kinase (PI3K). In other cell types, cytokines that activate the PI3K signaling pathway promote cell survival. Therefore we investigated whether there was an effect of SP-A on apoptosis as measured by DNA laddering, FACS analysis, TUNEL assay, and annexin V binding. SP-A protected primary cultures of rat type II alveolar cells against the apoptotic effects of etoposide and UV light and also protected the H441 human Clara lung tumor cell line against staurosporine-induced apoptosis. The protective effects of SP-A were abrogated by inhibition of either tyrosine-specific Protein kinase activity or PI3K. SP-A/SPAR interaction thus initiates a signaling pathway that regulates apoptosis in type II cells. These findings may be important in understanding the pathogenesis of acute lung injury and pulmonary tumorigenesis and may suggest new therapeutic options.

Stephen S Hecht - One of the best experts on this subject based on the ideXlab platform.

  • indole 3 carbinol inhibits 4 methylnitrosamino 1 3 pyridyl 1 butanone plus benzo a pyrene induced lung tumorigenesis in a j mice and modulates carcinogen induced alterations in Protein levels
    Cancer Research, 2007
    Co-Authors: Fekadu Kassie, Lorraine B Anderson, Robyn M Scherber, David Lahti, Pramod Upadhyaya, Stephen S Hecht
    Abstract:

    We tested the chemopreventive efficacy of indole-3-carbinol (I3C), a constituent of Brassica vegetables, and its major condensation product, 3,3′-diindolylmethane (DIM), against lung tumorigenesis induced by a mixture of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[ a ]pyrene (BaP) in A/J mice. The mixture of NNK plus BaP (2 μmol each) was administered by gavage as eight weekly doses, whereas I3C (112 μmol/g diet) and DIM (2 and 30 μmol/g diet in experiments 1 and 2, respectively) were given in the diet for 23 weeks beginning at 50% of carcinogen treatment. I3C reduced NNK plus BaP–induced tumor multiplicity by 78% in experiment 1 and 86% in experiment 2; the respective reductions in tumor multiplicity by DIM were 5% and 66%. Using a quantitative proteomics method, isobaric tags for relative and absolute quantitation (iTRAQ) coupled with mass spectrometry, we identified and quantified at least 250 Proteins in lung tissues. Of these Proteins, nine showed differences in relative abundance in lung tissues of carcinogen-treated versus untreated mice: fatty acid synthase, transketolase, pulmonary Surfactant-Associated Protein C (SP-C), l-plastin, annexin A1, and haptoglobin increased, whereas transferrin, α-1-antitrypsin, and apolipoProtein A-1 decreased. Supplementation of the diet of carcinogen-treated mice with I3C reduced the level of SP-C, l-plastin, annexin A1, and haptoglobin to that of untreated controls. These results were verified using immunoblotting. We show here that tumor-Associated signature Proteins are increased during NNK plus BaP–induced lung carcinogenesis, and I3C inhibits this effect, suggesting that the lung tumor chemopreventive activity of I3C might be related to modulation of carcinogen-induced alterations in Protein levels. [Cancer Res 2007;67(13):6502–11]