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Biochimica Et Biophysica Acta Nov 1998Surfactant protein B is a small homodimeric protein that is found tightly associated with surfactant lipids in the alveolar space. In this review, we discuss the actions... (Review)
Review
Surfactant protein B is a small homodimeric protein that is found tightly associated with surfactant lipids in the alveolar space. In this review, we discuss the actions of SP-B on phospholipid membranes using information predominantly obtained from model membrane systems. We try to correlate these model actions with current concepts of SP-B structure and proposed biological functions. These functions may include critical roles in the intracellular assembly of surfactant through a role in lamellar body organogenesis, the structural rearrangement of secreted surfactant lipids into tubular myelin, and the subsequent rapid insertion of secreted surfactant phospholipids into the surface film itself. The relevance of SP-B to human biology is emphasized by the fatal respiratory distress that is associated with a genetic deficiency of SP-B and the important role of SP-B in certain exogenous surfactant formulations in wide clinical use.
Topics: Lipid Bilayers; Liposomes; Protein Binding; Protein Precursors; Protein Processing, Post-Translational; Protein Structure, Secondary; Protein Structure, Tertiary; Proteolipids; Pulmonary Surfactants
PubMed: 9813296
DOI: 10.1016/s0925-4439(98)00064-7 -
Journal of Lipid Research Nov 1981A technique is described for isolating lamellar body material from rat lung. Membranes with relative densities ranging between 1.050 and 1.074 g/ml were isolated by...
A technique is described for isolating lamellar body material from rat lung. Membranes with relative densities ranging between 1.050 and 1.074 g/ml were isolated by centrifugation of crude lung homogenates upward through continuous linear sucrose gradients at 40,000 rpm (199,000 g) for 3 hr. Their protein and lipid content was characteristic of that of lamellar bodies. They were free of contaminating microsomal and mitochondrial marker enzymes but contained enzyme activities associated with lysosomes and Golgi complex. Longer or repeated centrifugation resulted in a reduced yield and an apparent transformation of some of the material to lower densities. Electron microscopy revealed that most of the images represent disrupted rather than intact lamellar bodies. Other methods for preparation of lamellar bodies entail either sedimentation or pelleting at interfaces between sucrose solutions. Such preparations are often contaminated with endoplasmic reticulum membranes and have apparently lost the more fragile bodies. The present technique reveals the heterogeneous nature of lamellar body material and should be useful in a search for lamellar body precursors and in the investigation of the mechanisms by which surfactant is synthesized or assembled.
Topics: Animals; Cell Fractionation; Centrifugation, Density Gradient; Freeze Fracturing; Lipids; Lung; Male; Microbodies; Microscopy, Electron; Organoids; Phospholipids; Proteins; Rats
PubMed: 7320637
DOI: No ID Found -
BioMed Research International 2013During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways... (Review)
Review
During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB. In the noncompliant avian lung, attenuation proceeds through cell-cutting processes that result in remarkable thinning of the epithelial layer. A host of morphoregulatory molecules, including transcription factors such as Nkx2.1, GATA, HNF-3, and WNT5a; signaling molecules including FGF, BMP-4, Shh, and TFG- β and extracellular proteins and their receptors have been implicated. During normal physiological function, the BGB may be remodeled in response to alterations in transmural pressures in both blood capillaries and airspaces. Such changes are mitigated through rapid expression of the relevant genes for extracellular matrix proteins and growth factors. While an appreciable amount of information regarding molecular control has been documented in the mammalian lung, very little is available on the avian lung.
Topics: Animals; Birds; Blood-Air Barrier; Capillaries; Humans; Intercellular Signaling Peptides and Proteins; Signal Transduction; Transcription Factors
PubMed: 23484070
DOI: 10.1155/2013/101597 -
Computational and Structural... 2022Acute respiratory distress syndrome (ARDS) could account for a considerable proportion of neonatal death, while the genetic etiology and pathophysiology of neonatal ARDS...
BACKGROUND
Acute respiratory distress syndrome (ARDS) could account for a considerable proportion of neonatal death, while the genetic etiology and pathophysiology of neonatal ARDS remain elusive. In this case-control study, 515 neonates were enrolled in the China Neonatal Genomes Project (CNGP, NCT03931707) from August 2016 to June 2021, including 196 ARDS and 319 non-ARDS matched by sex, gestational age, birth weight, perinatal asphyxia, pneumonia, sepsis, and necrotizing enterocolitis. Clinical exome sequencing was used to detect genetic variants. Collapsing analyses together with permutation tests were used to identify ARDS risk genes enriched for rare variants in ARDS samples. In silico functional interaction analysis and expression pattern studies at different stages of lung development were used to investigate the biological functions of the risk genes.
RESULTS
Collapsing analyses identified that rare variants were significantly abundant in the genes associated with the precursor of the lamellar body and there were eight predicted risk genes with strong confidence ( < 0.01). Among them, the expression of increased significantly in lung development and was up-regulated in ARDS ( < 0.05). In addition, 151 predicted transcriptional target proteins of were highly enriched in the lamellar body responsible for pulmonary surfactant storage and secretion.
CONCLUSIONS
In our study, the genes associated with pulmonary surfactant storage and release were highly enriched with rare variants. A novel neonatal ARDS risk gene may be a key gene for neonatal lung development and pulmonary surfactant homeostasis. Additional validation in independent patient populations and further exploration of underlying molecular mechanisms are warranted.
PubMed: 36187926
DOI: 10.1016/j.csbj.2022.08.055 -
Cellular Physiology and Biochemistry :... 2010The surfactant system of the lung has essential biophysical and immunomodulatory functions. Only at the electron microscopic level does surfactant reveal its... (Review)
Review
The surfactant system of the lung has essential biophysical and immunomodulatory functions. Only at the electron microscopic level does surfactant reveal its morphological complexity--and beauty. Therefore, morphological tools are indispensible to characterize the surfactant system in health and disease. Stereology provides the gold standard for obtaining quantitative (morphometric) data in microscopy. The combination of microscopy and stereology allows for qualitative and quantitative analysis of the intraalveolar as well as the intracellular surfactant pool, both in its preserved microorganization and localization within the lung. Surfactant-producing alveolar epithelial type II cells can be counted and sampled for size estimation with physical disectors at a high magnification light microscopic level. The number of their surfactant storing lamellar bodies can be estimated using physical disectors at the electron microscopic level. Electron tomography allows for high resolution 3D visualization of lamellar body fusion pores. Intraalveolar surfactant subtypes can be quantitated in situ, thus reflecting the functional state of the intraalveolar surfactant pool. By immunoelectron microscopy, surfactant protein distribution can be analyzed. These methods allow for a comprehensive quantitative analysis of surfactant (ultra-)structure. Here, we give an overview on the analysis of the normal and disordered surfactant system by electron microscopy and stereology.
Topics: Alveolar Epithelial Cells; Animals; Humans; Microscopy, Electron; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Secretory Vesicles
PubMed: 20054142
DOI: 10.1159/000272061 -
Acta Dermato-venereologica Nov 2015Wet wrap therapy, based on skin application of a double layer of tubular bandages or gauze with a moist first inner layer and a dry second outer layer, is utilized to... (Review)
Review
Wet wrap therapy, based on skin application of a double layer of tubular bandages or gauze with a moist first inner layer and a dry second outer layer, is utilized to treat various pruritic conditions, in particular severe and refractory atopic dermatitis. This review, by literature search, evaluates current knowledge about wet wrap therapy. Wet wrap therapy superimposed topical corticosteroids appears more efficient than emollients only, at least for short-time treatments. Despite higher efficacy, there is a tendency towards more frequent infections when topical corticosteroids are covered with wet wrap bandages compared to emollients only. While temporary suppression of hypothalamic-pituitary-adrenocortical-axis was seen due to systemic bioactivity of corticosteroids, no long-term observation studies on putative adverse effects were identified. One hypothesis suggests that wet wrap therapy may trigger increased lamellar body secretion resulting in recovery of the damaged intercellular lipid laminar structure. Otherwise, little investigation on mechanisms exists.
Topics: Administration, Topical; Adrenal Cortex Hormones; Bandages; Dermatitis, Atopic; Emollients; Humans; Skin Diseases; Water
PubMed: 25940919
DOI: 10.2340/00015555-2134 -
The Journal of Investigative Dermatology Oct 2001We propose that skin barrier morphogenesis may take place via a continuous and highly dynamic process of intersection-free membrane unfolding with a concomitant... (Review)
Review
We propose that skin barrier morphogenesis may take place via a continuous and highly dynamic process of intersection-free membrane unfolding with a concomitant crystallization of the emerging multilamellar lipid structure representing the developing skin barrier. This implies that the trans-Golgi network and lamellar bodies of the uppermost stratum granulosum cells as well as the multilamellar lipid matrix of the intercellular space at the border zone between stratum granulosum and stratum corneum could be representations of one and the same continuous membrane structure. The profound difference between the earlier Landmann model and the membrane folding model presented here is that the Landmann model includes changes in membrane topology, whereas topology is kept constant during skin barrier formation according to the membrane folding model. The main advantages of the membrane folding model with respect to the Landmann model are the following: (i) smaller energy cost (involves no budding or fusion); (ii) conserves membrane continuity (preserves water compartmentalization and allows control hereof; membrane continuity essential for barrier function); (iii) allows meticulous control (the thermodynamics of the unfolding procedure are related to curvature energy); (iv) faster (milliseconds, as membrane unfolding basically represents a phase transition from cubic-like to lamellar morphology; involves no budding or fusion); (v) membrane folding between lamellar and cubic-like morphologies has been identified in numerous biologic systems; (vi) there is experimental evidence for an "extensive intracellular tubulo-reticular cisternal membrane system within the apical cytosol of the outermost stratum granulosum"; and (vii) may explain the reported plethora of forms, numbers, sizes and general appearances of "lamellar bodies" in transmission electron microscopy micrographs.
Topics: Animals; Crystallization; Humans; Membranes; Models, Biological; Skin Physiological Phenomena
PubMed: 11676818
DOI: 10.1046/j.0022-202x.2001.01445.x -
Genes & Development Aug 2022Stem cells are fundamental units of tissue remodeling whose functions are dictated by lineage-specific transcription factors. Home to epidermal stem cells and their...
Stem cells are fundamental units of tissue remodeling whose functions are dictated by lineage-specific transcription factors. Home to epidermal stem cells and their upward-stratifying progenies, skin relies on its secretory functions to form the outermost protective barrier, of which a transcriptional orchestrator has been elusive. KLF5 is a Krüppel-like transcription factor broadly involved in development and regeneration whose lineage specificity, if any, remains unclear. Here we report KLF5 specifically marks the epidermis, and its deletion leads to skin barrier dysfunction in vivo. Lipid envelopes and secretory lamellar bodies are defective in KLF5-deficient skin, accompanied by preferential loss of complex sphingolipids. KLF5 binds to and transcriptionally regulates genes encoding rate-limiting sphingolipid metabolism enzymes. Remarkably, skin barrier defects elicited by KLF5 ablation can be rescued by dietary interventions. Finally, we found that KLF5 is widely suppressed in human diseases with disrupted epidermal secretion, and its regulation of sphingolipid metabolism is conserved in human skin. Altogether, we established KLF5 as a disease-relevant transcription factor governing sphingolipid metabolism and barrier function in the skin, likely representing a long-sought secretory lineage-defining factor across tissue types.
PubMed: 36008138
DOI: 10.1101/gad.349662.122 -
Histochemistry and Cell Biology Oct 2010Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on...
Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recycling.
Topics: Animals; Artifacts; Cryoelectron Microscopy; Cryopreservation; Cryoultramicrotomy; Fluorocarbons; Freeze Substitution; Freezing; Ice; Image Processing, Computer-Assisted; Mice; Mice, Inbred BALB C; Pressure; Pulmonary Alveoli; Pulmonary Surfactants; Secretory Vesicles; Staining and Labeling; Tissue Fixation; Vitrification
PubMed: 20809233
DOI: 10.1007/s00418-010-0736-4 -
Toxicology and Applied Pharmacology May 2021With the rapid increase in application of disinfectants worldwide as a method to block the spread of coronavirus, many new products are being introduced into the market...
With the rapid increase in application of disinfectants worldwide as a method to block the spread of coronavirus, many new products are being introduced into the market without thorough verification of their impacts on human health and the environment. In the present study, we aimed to propose a screening marker for materials that can induce fibrotic lung disease using disinfectants, which had been demonstrated as causative materials of chronic inflammation and interstitial fibrosis. We first calculated the corresponding LC level based on results from cell viability test and exposed the LC level of disinfectants to human bronchial epithelial cells for 24 h. Formation of lamellar body-like structures, cleavage of the nuclear matrix, structural damage of mitochondria were found in the cytosol of the treated cells. We also dosed disinfectants by pharyngeal aspiration to mice to determine the LD0 level. The mice were sacrificed on Day 14 after a single dosing, and lamellar body-like structures were observed in the lung tissue of mice. Herein, we hypothesize that DNA damage and metabolic disturbance may play central roles in disinfectant-induced adverse health effects. Additionally, we propose that formation of lamellar bodies can be a screening marker for interstitial fibrosis.
Topics: Animals; Biomarkers; Cell Line; Cell Survival; Disinfectants; Epithelial Cells; Female; Humans; Intracellular Fluid; Lung Diseases, Interstitial; Mice; Mice, Inbred ICR; Pulmonary Fibrosis
PubMed: 33771551
DOI: 10.1016/j.taap.2021.115501