Επιφανειοδραστικός παράγοντας

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Joanna Floros, Ph.D Evan Pugh Professor, Departments of Cellular and Molecular Physiology, Pediatrics, and Obstetrics and Gynecology. The Pennsylvania State University, College of Medicine, Hershey, PA, U.S.A Surfactant Composition and Function 8 th World Hellenic Biomedical Congress

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Transcript of Επιφανειοδραστικός παράγοντας

  • Joanna Floros, Ph.D

    Evan Pugh Professor, Departments of Cellular and Molecular Physiology, Pediatrics, and Obstetrics and Gynecology.

    The Pennsylvania State University, College of Medicine, Hershey, PA, U.S.ASurfactant Composition and Function8th World Hellenic Biomedical Congress

  • 1. Characteristics of SurfactantWhat is surfactant?What is its composition?Where is it made?What is its structure?Surfactant2. Function of surfactant

  • MAJOR CONSTITUENTS OF PULMONARY SURFACTANTPC(DSPC)CholesterolPGPIOther lipidsProteinPESurfactantSP-ASP-BSP-C ProteinsUnsaturatedOther ProteinsSP-DPulmonary surfactant biochemically, is a lipoprotein complex that lines the internal surface of the alveoli.What is Pulmonary Surfactant and What is its Composition?16:/16:0PC

  • Fishman 2-19

  • SURFACTANT HETEROGENEITY AND LIFE CYCLESMALL AGGREGATESLARGE AGGREGATESSURFACE FILMTUBULAR MYELINLAMELLAR BODIESHYPOPHASE FLUID(SUPERNATANT)SP-ALB, TM, SP-A

  • 1. Characteristics of SurfactantWhat is surfactant?What is its composition?Where is it made?What is its structure?Surfactant2. Function of surfactant and/or surfactant components Lowering of surface tension.

    Innate host defense.

    Initiation of parturition (SP-A, a hormone?)

  • Functions of surfactantStabilizes alveoli and prevents alveolar (lung) collapse with each exhalation by lowering the surface tension at the air-liquid surface.

    Surfactant components play a role in host defense and protect the lung from injuries or infections caused by inhaled microorganisms, particles, toxins, other.

    One of the protein component of surfactant (SP-A) may serve as a hormone in parturition. Surface tensionHost defenseInitiation of labor

  • J. KendingAir-Liquid InterfaceWithout surfactantWith surfactantSurfactant

  • MAJOR CONSTITUENTS OF PULMONARY SURFACTANTPC(DSPC)CholesterolPGPIOther lipidsProteinPESurfactantSP-ASP-BSP-C ProteinsUnsaturatedOther ProteinsSP-D16:0/16:0PC

  • Functions of surfactantStabilizes alveoli and prevents alveolar (lung) collapse with each exhalation by lowering the surface tension at the air-liquid surface.

    Surfactant components play a role in host defense and protect the lung from injuries or infections caused by inhaled microorganisms, particles, toxins, other.

    One of the protein component of surfactant (SP-A) may serve as a hormone in parturition. Surface tensionHost defenseInitiation of labor

  • INHIBITIONSP-ALIPIDStimulationInhibitionOxidant ProductionSplenocyte ProliferationCell Surface MarkersCytokine ProductionNF-kB ActivationFibroblast ApoptosisCollagen and Collagenase ProductionSP-APESMPCPGPISTIMULATIONCHOLPCPGPIINHIBITIONSURFACTANT REGULATION OF IMMUNE CELLSSTIMULATION

  • LARGE AGGREGATESTUBULAR MYELINSP-ACell Surface Markers;Cytokine Production;NF-kB Activation;Collagen and Collagenase ProductionSurfactant-related Host defense-relatedSP-A FUNCTIONInnateAdaptivemyr800700600500presentRegulation of inflammatory processesInnate Immunity

  • Human SP-A Genes, and Variants Genes6A21A0CTPSP-A1SP-A2VariantsThe above variants have been shown to exhibit qualitative and quantitative differences.In addition environmental insults, such as ozone, appear to differentially alter their functional activity and thus contribute to individual differences in disease susceptibility.

  • Differences exist among SP-A variants in their ability to enhance phagocytosis of bacteria by alveolar macrophages in the presence or absence of environmentalfactors.

  • EXPERIMENTAL APPROACH

  • Microscopic view of live P. aeruginosa, phagocytized by rat alveolar macrophages in the presence or absence of human SP-A R E S U L T S

  • SP-A2 products exhibit higher phagocytic ability than SP-A1Mammalian expressed variants100200300400500Phagocytic index (%)1.56 mg/mln=5** *****SP-A21A01A 6A26A4SP-A1hSP-A

  • Ability of SP-A variants to enhance phagocytosis by alveolar macrophages following exposure to ozone. 1A0 > 1A0 (SP-A2) 6A4 = 6A4 (SP-A1) 1A0/6A4 > 1A0/6A4 (SP-A2/SP-A1) Ozone-exposedUnexposed

  • Functions of surfactantStabilizes alveoli and prevents alveolar (lung) collapse with each exhalation by lowering the surface tension at the air-liquid surface.

    Surfactant components play a role in host defense and protect the lung from injuries or infections caused by inhaled microorganisms, particles, toxins, other.

    One of the protein component of surfactant (SP-A) may serve as a hormone in parturition. Surface tensionHost defenseInitiation of labor

  • Increased levels of SP-AFetal macrophages activateIncreased levels of proinflammatory cytokines (i.e. IL-b1)NF-kBIncrease expression of genes thatcause myometrial contractibilityactivateSurfactant lipids(Arachidonate derivatives)P65 antagonizes progesterone receptor activation of genes that modulateuterine quiescence.Prostaglandin synthesisFetal SP-A initiates labor

  • SummaryPulmonary surfactant, a lipoprotein complex, is essential throughout life for normal lung function, host defense, and other functions.

    Derangement in surfactant either through alterations in composition or modification (i.e. oxidation) can negatively affect normal lung function and host defense.

    Genetic differences in surfactant components may contribute to differences in disease risk among individuals.

    LEGEND Fishman Figure 2-19 A type II epithelial cell from the human lung forms junction (J) with type I epithelial cells (EP1). Its cytoplasm contains osmiophilic lamellar bodies (LB) and a rich complement of organelles: mitochondria (M), endoplasmic reticulum (ER), and so on. The nucleus (N) is surrounded by a perinuclear cisterna (pNC) which is perforated by nuclear pores (NP). BM = basement membrane; F = fibroblast; MV = microvilli; A = alveolus.