joanna floros, ph.d evan pugh professor, departments of cellular and molecular physiology,...
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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
8th World Hellenic Biomedical Congress
1. Characteristics of Surfactant
• What is surfactant?
• What is its composition?
• Where is it made?
• What is its structure?
Surfactant
2. Function of surfactant
MAJOR CONSTITUENTS OF PULMONARY SURFACTANT
PC
(DSPC)
Cholesterol PG PIOther lipids
Protein
PE
Surfactant
SP-ASP-BSP-C
Proteins
Unsaturated
Other Proteins
SP-D
Pulmonary surfactant biochemically, is a lipoprotein complex that lines the internal surface of the alveoli.
What is Pulmonary Surfactant and What is its Composition?
16:/16:0
PC
SURFACTANT HETEROGENEITY AND LIFE CYCLE
SMALL AGGREGATES
LARGE AGGREGATES
SURFACE FILM
TUBULAR MYELINLAMELLAR BODIES
HYPOPHASE FLUID
(SUPERNATANT)
SP-A
LB, TM, SP-A
1. Characteristics of Surfactant
• What is surfactant?• What is its composition?• Where is it made?• What is its structure?
Surfactant
2. Function of surfactant and/or surfactant components
• Lowering of surface tension.
• Innate host defense.
• Initiation of parturition (SP-A, a hormone?)
Functions of surfactant
• Stabilizes 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 tension
Host defense
Initiation of labor
MAJOR CONSTITUENTS OF PULMONARY SURFACTANT
PC
(DSPC)
Cholesterol PG PIOther lipids
Protein
PE
Surfactant
SP-ASP-BSP-C
Proteins
Unsaturated
Other Proteins
SP-D
16:0/16:0
PC
Functions of surfactant
• Stabilizes 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 tension
Host defense
Initiation of labor
INHIBITION
SP-A LIPID
Stimulation Inhibition
Oxidant ProductionSplenocyte Proliferation
Cell Surface MarkersCytokine Production
NF-kB ActivationFibroblast Apoptosis
Collagen and Collagenase Production
SP-A
PESM
PCPGPI
STIMULATION
CHOL
PCPG
PI
INHIBITION
SP-A
PESM
CHOL
SURFACTANT REGULATION OF IMMUNE CELLS
STIMULATION
LARGE AGGREGATES
TUBULAR MYELIN
SP-A
Cell Surface Markers;Cytokine Production;
NF-kB Activation;Collagen and Collagenase
Production
Surfactant-related Host defense-related
SP-A FUNCTION
Innate Adaptive
myr800 700 600 500 present
Regulation of inflammatory processes
Innate Immunity
Human SP-A Genes, and Variants
Genes
6A21A0
C TP SP-A1SP-A2
Variants
The 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.
agar plateagar plate suspensionsuspensionof bacteria of bacteria
alveolar macrophagesalveolar macrophages
SP-ASP-Aphagocytosisphagocytosis
wash off free wash off free bacteriabacteria
slide slide preparationpreparation
light light microscopy microscopy
analysisanalysis
BALBAL
insect cells orinsect cells ormammalian cellsmammalian cells
ratrat
ozoneozone
EXPERIMENTAL APPROACH EXPERIMENTAL APPROACH
Microscopic view of live P. aeruginosa, phagocytized by rat alveolar macrophages in the presence or absence of human SP-A
No SP-A SP-A
R E S U L T SR E S U L T S
SP-A2 products exhibit higher phagocytic ability than SP-A1
§ hSP-A vs. SP-A variants (insect)
Phagocytic index: % of bacteria-positive AMs the average # of bacteria per bacteria-positive AMs
* SP-A2 vs. SP-A1 ; ** 6A2 vs. 6A4 ; *** hSP-A vs. 6A4 (mammalian); (hSP-A: 25 µg/ml)
Mikerov et al
Bacteria: P.aeruginosa
Mammalian expressed variantsMammalian expressed variants
100
200
300
400
500
Ph
ago
cyti
c in
dex
(%
)
1.56 g/ml n=5
**
***
**
SP-A2
1A0 1A 6A2 6A4
SP-A1
hSP-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 surfactant
• Stabilizes 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 tension
Host defense
Initiation of labor
Increased levels of SP-A
Fetal macrophages
activate
Increased levels of proinflammatory cytokines (i.e. IL-b1)
NF-kB
Increase expression of genes thatcause myometrial contractibility
activate
Surfactant lipids(Arachidonate derivatives)
P65 antagonizes progesterone receptor activation of genes that modulateuterine quiescence.
Prostaglandin synthesis
Fetal SP-A initiates labor
Summary
• Pulmonary 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.
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