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Biochimica Et Biophysica Acta Nov 1998The surfactant components saturated phosphatidylcholine, SP-B and SP-C, are secreted together in lamellar bodies, and at least a part of the de novo synthesized SP-A is... (Review)
Review
The surfactant components saturated phosphatidylcholine, SP-B and SP-C, are secreted together in lamellar bodies, and at least a part of the de novo synthesized SP-A is secreted independently. The surface film forms from tubular myelin and loose lipid arrays, and it generates unilamellar vesicles that lack surfactant proteins and are thought to represent catabolic forms. The half-life values for the clearance of surfactant proteins from lungs range from 6.5 to 28 h and vary with species. There is minimal information about the associations of the surfactant proteins with lipids or with each other after film formation, although all surfactant components seem to be recycled back into lamellar bodies in type II cells. The relative importance of type II cells or macrophages to the catabolism of the protein components of surfactant remains to be characterized, as do regulators of surfactant homeostasis.
Topics: Animals; Half-Life; Mice; Phosphatidylcholines; Proteolipids; Pulmonary Alveoli; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Rabbits
PubMed: 9813337
DOI: 10.1016/s0925-4439(98)00069-6 -
Molecular Cell Jan 2021Breathing depends on pulmonary surfactant, a mixture of phospholipids and proteins, secreted by alveolar type II cells. Surfactant requires lamellar bodies (LBs),...
Breathing depends on pulmonary surfactant, a mixture of phospholipids and proteins, secreted by alveolar type II cells. Surfactant requires lamellar bodies (LBs), organelles containing densely packed concentric membrane layers, for storage and secretion. LB biogenesis remains mysterious but requires surfactant protein B (SP-B), which is synthesized as a precursor (pre-proSP-B) that is cleaved during trafficking into three related proteins. Here, we elucidate the functions and cooperation of these proteins in LB formation. We show that the N-terminal domain of proSP-B is a phospholipid-binding and -transfer protein whose activities are required for proSP-B export from the endoplasmic reticulum (ER) and sorting to LBs, the conversion of proSP-B into lipoprotein particles, and neonatal viability in mice. The C-terminal domain facilitates ER export of proSP-B. The mature middle domain, generated after proteolytic cleavage of proSP-B, generates the striking membrane layers characteristic of LBs. Together, our results lead to a mechanistic model of LB biogenesis.
Topics: Animals; Endoplasmic Reticulum; Female; HEK293 Cells; Humans; Lipoproteins; Mice; Multiprotein Complexes; Protein Domains; Pulmonary Surfactant-Associated Protein B
PubMed: 33242393
DOI: 10.1016/j.molcel.2020.10.042 -
Journal of Lipid Research Oct 1991This review article attempts to present an overview of the occurrence and function of lipid storage and secretory organelles: the lamellar bodies. Morphologically these... (Review)
Review
This review article attempts to present an overview of the occurrence and function of lipid storage and secretory organelles: the lamellar bodies. Morphologically these organelles vary considerably in size (100 nm to 2400 nm); they are surrounded by a membrane and contain multilamellar lipid membranes. Lamellar bodies may also contain apolipoproteins and lytic enzymes and have an acidic pH, which confers on them a lysosomal character. Under normal physiological conditions, the main function of lamellar bodies is the supply of extracellular domains with specialized lipid components related to a specialized function. The lamellar bodies of the lung epithelium are best investigated in their functional and structural features and are the storage form of the lung surfactant. They provide a monomolecular lipid film of dipalmitoyl phosphatidylcholine (DPPC) on the surface of lung alveoli to lower surface tension necessary for optimal gas exchange and a hydrophobic protective lining against environmental influences. Additional cells of the respiratory system such as the mucosa of the human nose and the bronchi contain lamellar bodies. Lamellar bodies are also found in the gastrointestinal tract, in tongue papillae, oral epithelium, and mucosa cells of the stomach. The major phospholipid of lamellar bodies in mucosa cells of the stomach is DPPC, providing a hydrophobic protective lipid film against the tissue-damaging activities of gastric juice. The hydrophobic water-protective barrier of the skin, which consists mainly of neutral lipids, however, also originates from lamellar bodies secreted by epithelial cells. Lamellar bodies, mainly consisting of DPPC, also occur in mesodermal cell layers of sliding surfaces to provide the lubrication of joints, of the peritoneum, pericardium, and pleural mesothelium. In certain pathological conditions, such as atherosclerosis, Niemann-Pick disease, lecithin:cholesterol acyltransferase (LCAT) deficiency, cholestasis, degeneration of nerves and brain, and regeneration of nerves and wound healing, lipid-containing lamellar bodies have been observed in various cells, the function of which still remains to be elucidated. In early and late lesions of atherosclerotic plaques, lamellar bodies, consisting of unesterified cholesterol and phospholipids, are associated with the extracellular matrix of the intima. During regression of fatty streaks, lamellar bodies are seen intracellularly in macrophages and smooth muscle cells. Inherited metabolic disorders, such as Niemann-Pick disease type I and type II, result in the excessive accumulation of lamellar body-containing cells, for example in bone marrow, spleen, and lymphoid tissue. Type I is a deficiency in sphingomyelinase and type II is a defect in intracellular trafficking of lipoprotein-derived cholesterol.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Gastric Mucosa; Humans; Lipid Metabolism; Lung; Nervous System; Organelles; Proteins
PubMed: 1797938
DOI: No ID Found -
Cellular Physiology and Biochemistry :... 2010A major function of the pulmonary alveolar type II cell is the secretion of surfactant, a lipoprotein-like substance, via exocytosis of secretory vesicles termed... (Review)
Review
A major function of the pulmonary alveolar type II cell is the secretion of surfactant, a lipoprotein-like substance, via exocytosis of secretory vesicles termed lamellar bodies (LBs). The process of surfactant secretion is remarkable in several aspects, considering stimulus-delayed fusion activity, poor solubility of vesicle contents, long hemifusion lifetimes, slow fusion pore expansion and active, actin-driven content release. Cell stretch as well as P2Y(2) receptor stimulation by extracellular ATP are considered the most potent stimuli for LB exocytosis. For both stimuli, elevation of the cytoplasmic Ca(2+) concentration [Ca(2+)](c) is a key step. This review summarizes possible physiological roles and pathways of stretch- or ATP-induced surfactant secretion and discusses molecular mechanisms controlling the pre-, hemi- and postfusion phase, in comparison with neuroendocrine release mechanisms.
Topics: Alveolar Epithelial Cells; Animals; Exocytosis; Humans; Pulmonary Surfactants; Receptors, Purinergic P2; Secretory Vesicles
PubMed: 20054140
DOI: 10.1159/000272046 -
Traffic (Copenhagen, Denmark) Jun 2019Lysosome-related organelles (LROs) comprise a diverse group of cell type-specific, membrane-bound subcellular organelles that derive at least in part from the... (Review)
Review
Lysosome-related organelles (LROs) comprise a diverse group of cell type-specific, membrane-bound subcellular organelles that derive at least in part from the endolysosomal system but that have unique contents, morphologies and functions to support specific physiological roles. They include: melanosomes that provide pigment to our eyes and skin; alpha and dense granules in platelets, and lytic granules in cytotoxic T cells and natural killer cells, which release effectors to regulate hemostasis and immunity; and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of LROs are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky-Pudlak syndromes. This review provides a comprehensive overview of LROs in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.
Topics: Animals; Hermanski-Pudlak Syndrome; Humans; Lysosomes; Melanosomes; Weibel-Palade Bodies
PubMed: 30945407
DOI: 10.1111/tra.12646 -
Acta Neuropathologica Communications Nov 2022CCCTC-binding factor (CTCF) has a key role in higher-order chromatin architecture that is important for establishing and maintaining cell identity by controlling gene...
CCCTC-binding factor (CTCF) has a key role in higher-order chromatin architecture that is important for establishing and maintaining cell identity by controlling gene expression. In the mature cerebellum, CTCF is highly expressed in Purkinje cells (PCs) as compared with other cerebellar neurons. The cerebellum plays an important role in motor function by regulating PCs, which are the sole output neurons, and defects in PCs cause motor dysfunction. However, the role of CTCF in PCs has not yet been explored. Here we found that the absence of CTCF in mouse PCs led to progressive motor dysfunction and abnormal dendritic morphology in those cells, which included dendritic self-avoidance defects and a proximal shift in the climbing fibre innervation territory on PC dendrites. Furthermore, we found the peculiar lamellar structures known as "giant lamellar bodies" (GLBs), which have been reported in PCs of patients with Werdnig-Hoffman disease, 13q deletion syndrome, and Krabbe disease. GLBs are localized to PC dendrites and are assumed to be associated with neurodegeneration. They have been noted, however, only in case reports following autopsy, and reports of their existence have been very limited. Here we show that GLBs were reproducibly formed in PC dendrites of a mouse model in which CTCF was deleted. GLBs were not noted in PC dendrites at infancy but instead developed over time. In conjunction with GLB development in PC dendrites, the endoplasmic reticulum was almost absent around the nuclei, the mitochondria were markedly swollen and their cristae had decreased drastically, and almost all PCs eventually disappeared as severe motor deficits manifested. Our results revealed the important role of CTCF during normal development and in maintaining PCs and provide new insights into the molecular mechanism of GLB formation during neurodegenerative disease.
Topics: Animals; Mice; Purkinje Cells; Lamellar Bodies; Neurodegenerative Diseases; Cerebellum; Dendrites
PubMed: 36447271
DOI: 10.1186/s40478-022-01478-6 -
Human Mutation Jul 2020ABCA3 transports phospholipids across lamellar body membranes in pulmonary alveolar type II cells and is required for surfactant assembly. Rare, biallelic, pathogenic...
ABCA3 transports phospholipids across lamellar body membranes in pulmonary alveolar type II cells and is required for surfactant assembly. Rare, biallelic, pathogenic ABCA3 variants result in lethal neonatal respiratory distress syndrome and childhood interstitial lung disease. Qualitative functional characterization of ABCA3 missense variants suggests two pathogenic classes: disrupted intracellular trafficking (type I mutant) or impaired ATPase-mediated phospholipid transport into the lamellar bodies (type II mutant). We qualitatively compared wild-type (WT-ABCA3) with four uncharacterized ABCA3 variants (c.418A>C;p.Asn140His, c.3609_3611delCTT;p.Phe1203del, c.3784A>G;p.Ser1262Gly, and c.4195G>A;p.Val1399Met) in A549 cells using protein processing, colocalization with intracellular organelles, lamellar body ultrastructure, and ATPase activity. We quantitatively measured lamellar body-like vesicle diameter and intracellular ABCA3 trafficking using fluorescence-based colocalization. Three ABCA3 variants (p.Asn140His, p.Ser1262Gly, and p.Val1399Met) were processed and trafficked normally and demonstrated well-organized lamellar body-like vesicles, but had reduced ATPase activity consistent with type II mutants. P.Phe1203del was processed normally, had reduced ATPase activity, and well-organized lamellar body-like vesicles, but quantitatively colocalized with both endoplasmic reticulum and lysosomal markers, an intermediate phenotype suggesting disruption of both intracellular trafficking and phospholipid transport. All ABCA3 mutants demonstrated mean vesicle diameters smaller than WT-ABCA3. Qualitative and quantitative functional characterization of ABCA3 variants informs mechanisms of pathogenicity.
Topics: A549 Cells; ATP-Binding Cassette Transporters; Cytoplasmic Vesicles; Humans; Lung Diseases, Interstitial; Mutation, Missense; Pulmonary Alveoli; Pulmonary Surfactants
PubMed: 32196812
DOI: 10.1002/humu.24014 -
Journal of Lipid Research Dec 2007The permeability barrier is required for terrestrial life and is localized to the stratum corneum, where extracellular lipid membranes inhibit water movement. The lipids... (Review)
Review
The permeability barrier is required for terrestrial life and is localized to the stratum corneum, where extracellular lipid membranes inhibit water movement. The lipids that constitute the extracellular matrix have a unique composition and are 50% ceramides, 25% cholesterol, and 15% free fatty acids. Essential fatty acid deficiency results in abnormalities in stratum corneum structure function. The lipids are delivered to the extracellular space by the secretion of lamellar bodies, which contain phospholipids, glucosylceramides, sphingomyelin, cholesterol, and enzymes. In the extracellular space, the lamellar body lipids are metabolized by enzymes to the lipids that form the lamellar membranes. The lipids contained in the lamellar bodies are derived from both epidermal lipid synthesis and extracutaneous sources. Inhibition of cholesterol, fatty acid, ceramide, or glucosylceramide synthesis adversely affects lamellar body formation, thereby impairing barrier homeostasis. Studies have further shown that the elongation and desaturation of fatty acids is also required for barrier homeostasis. The mechanisms that mediate the uptake of extracutaneous lipids by the epidermis are unknown, but keratinocytes express LDL and scavenger receptor class B type 1, fatty acid transport proteins, and CD36. Topical application of physiologic lipids can improve permeability barrier homeostasis and has been useful in the treatment of cutaneous disorders.
Topics: Animals; Cell Membrane; Cell Membrane Permeability; Epidermis; Fatty Acids; Humans; Lipids; Models, Biological; Skin
PubMed: 17872588
DOI: 10.1194/jlr.R700013-JLR200 -
Diving and Hyperbaric Medicine Sep 2018Since decompression sickness (DCS) in humans was first described, mankind has embarked on an odyssey to prevent it. The demonstration that decompression releases...
Since decompression sickness (DCS) in humans was first described, mankind has embarked on an odyssey to prevent it. The demonstration that decompression releases bubbles, which mainly contain inert gas (nitrogen, helium), into the circulation and that the slower the decompression rate the lesser the incidence of DCS, resulted in 1908 in the publication of the first, reasonably safe diving tables. Besides the development of proper diving tables, the selection of divers is also of importance. A relationship between body composition and DCS was observed in dogs as long ago as the nineteenth century, an observation supported early in the twentieth century: "Really fat men should never be allowed to work in compressed air, and plump men should be excluded from high pressure caissons…or in diving to more than about 10 fathoms, and at this depth the time of their exposure should be curtailed. If deep diving is to be undertaken…. skinny men should be selected." Alas, nothing is that simple! From my own experience it was not always the fat diver who ended up in the treatment chamber with DCS. Therefore, other factors must be at play; gender, age, physical fitness, and the existence of a persistent foramen ovale (PFO) have all been studied as possible factors for the development of vascular gas bubbles and, therefore, for DCS. However, none of these factors, alone or in combination, explain why there are intra-individual or intra-cohort differences in bubble grades (BG). In other words, why does a dive I did today led to a high BG but the same dive next week lead to a low one? Or, why is there such a difference in BG amongst divers of more or less the same age, gender, body composition and physical fitness? In a letter in this issue, a novel hypothesis is postulated that may fill in these gaps; active hydrophobic spots (AHS). These AHS can be found at the luminal side of capillary, venous and arterial walls and have an oligolamellar lining. In an in vitro experiment, nanobubbles developed on AHS after a 'dive' to 1,000 kPa (90 msw). It appears that AHS consist of dipalmitoylphosphatidylcholine (DPPC), which is the main component of surfactant. It is proposed that DPPC may leak from the alveoli into the alveolar capillary and be transported to veins and arteries where it precipitates and forms AHS. Based on these ideas, it is hypothesized that AHS generate nanobubbles that can grow into microbubbles. When these microbubbles detach from the AHS they might also take along pieces of the AHS membrane making the AHS smaller or even disappear. This phenomenon could explain some of the earlier findings regarding the formation of microbubbles in divers. The fact that the presence of microbubbles differs between younger and older divers, after repetitive dives, and between experienced divers and novice divers can be explained by this model, and AHS may be the missing link we are looking for in our quest to understand and treat DCS. However, some reservations must be made. Firstly, these observations are derived from in vitro and animal experiments and whether or not they reflect a similar process in man remains unclear. Secondly, it appears that female divers have lower bubble grades after similar dives compared to male divers, suggesting lower decompression stress. If AHS is the main generator for microbubbles, there should be a difference in the presence of AHS between men and women. We do not know from these animal experiments whether there is a gender difference, neither does a literature search in PubMed provide us with an answer. Thirdly, as said before, DPPC is the main component of surfactant. All alveolar surfactant phospholipids, such as DPPC, are secreted to the alveolar space via exocystosis of the lamellar bodies (LB) from alveolar type II (ATII) cells. To form a functional air-blood barrier, alveolar type I and ATII cells are connected to each other by tight junctions. These tight junctions constitute the seal of the intercellular cleft and in that way form a true barrier between the alveolus and the capillary. Only small molecules like oxygen, carbon dioxide, etc. can penetrate through this barrier by themselves due to passive diffusion. All other (macro)molecules, including DPPC, need intermediate processes such as ion transport proteins, channels, metabolic pumps, etc. to gain access to the pulmonary capillary lumen. To my knowledge, no such mechanisms for DPPC or LB are known. A theoretical explanation might be the fact that the production of DPPC and the exocystosis of DPPC-containing LBs into the alveolar space can be stimulated by stretch. Stretch of the alveoli can switch on Ca2+ entry by either mechanosensitive channels, store-operated channels or second messenger-operated channels, which induces LB exocystosis. Furthermore, an ATP-release mechanism might also be responsible for the pulmonary alveolar mechanotransduction of LB. During diving, transpulmonary pressure changes occur which might induce additional alveolar stretch and thus, theoretically, an extra release of LB. However, whether or not such exocystosis of LB is vascularly orientated remains unclear. Besides which, the leakage of DPPC from the alveolus to the pulmonary capillary might also be as simple as a malfunction of the tight junction due to epithelial membrane damage as a result of diving. Finally, it is also possible that DPPC is produced in other non-ATII cells in our body of which we are currently unaware. To conclude, this is an interesting hypothesis regarding the origin of microbubbles. Whether or not DPPC and LB are the main reason for individual sensitivity to DCS remains unclear. Further research will hopefully identify if DPPC and LB are indeed the missing link or just another branch on the big tree of the genesis of decompression sickness.
Topics: Body Composition; Decompression; Decompression Sickness; Diving; Female; Helium; Humans; Male; Mechanotransduction, Cellular; Oxygen
PubMed: 30199886
DOI: 10.28920/dhm48.3.130-131 -
Clinical, Cosmetic and Investigational... 2023The skin barrier is the first line of defense of the body, while skin lipids play an important role in the skin permeability barrier. Lamellar bodies are also involved...
BACKGROUND
The skin barrier is the first line of defense of the body, while skin lipids play an important role in the skin permeability barrier. Lamellar bodies are also involved in maintaining the stability of the skin permeability barrier. However, the exact origin of lamellar bodies remains unclear. Recent studies have suggested that autophagy may participate in the formation of lamellar bodies.
AIM
This study aimed to investigate the role of autophagy in the formation of lamellar bodies in keratinocytes and the regulation of keratinocyte lipids.
METHODS
Keratinocytes were incubated with autophagy inducer Rapamycin and autophagy inhibitor Bafilomycin A1. The changes in autophagy flux were detected by Western blot, and the formation of lamellar bodies was observed by transmission electron microscopy. Furthermore, the changes in keratinocytes lipidomics were detected by liquid chromatography-mass spectrometry.
RESULTS
Our research showed that the autophagy inducer promoted autophagy activation and formation of lamellar bodies in keratinocytes, while the inhibitor inhibited autophagy signals and the formation of lamellar bodies in keratinocytes. In addition, the lipidomics results revealed a significant change in glycerophospholipids after autophagy induction and autophagy inhibition.
CONCLUSION
These results demonstrate that autophagy may play an essential role in skin lipids via glycerophospholipids pathway.
PubMed: 37359719
DOI: 10.2147/CCID.S410252