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Frontiers in Cell and Developmental... 2021Epidermal lamellar bodies (eLBs) are secretory organelles that carry a wide variety of secretory cargo required for skin homeostasis. eLBs belong to the class of... (Review)
Review
Epidermal lamellar bodies (eLBs) are secretory organelles that carry a wide variety of secretory cargo required for skin homeostasis. eLBs belong to the class of lysosome-related organelles (LROs), which are cell-type-specific organelles that perform diverse functions. The formation of eLBs is thought to be related to that of other LROs, which are formed either through the gradual maturation of Golgi/endosomal precursors or by the conversion of conventional lysosomes. Current evidence suggests that eLB biogenesis presumably initiate from -Golgi network and receive cargo from endosomes, and also acquire lysosome characteristics during maturation. These multistep biogenesis processes are frequently disrupted in human skin disorders. However, many gaps remain in our understanding of eLB biogenesis and their relationship to skin diseases. Here, we describe our current understanding on eLB biogenesis with a focus on cargo transport to this LRO and highlight key areas where future research is needed.
PubMed: 34458262
DOI: 10.3389/fcell.2021.701950 -
Cells Dec 2021The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific... (Review)
Review
The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of surface tension and stabilization of alveoli during respiration. Its lack or deficiency may cause various forms of respiratory distress syndrome (RDS). Surfactant is also part of the innate immune system in the lung, defending the organism against air-borne pathogens. The limiting (organelle) membrane that encloses the LB contains various transporters that are in part responsible for translocating lipids and other organic material into the LB. On the other hand, this membrane contains ion transporters and channels that maintain a specific internal ion composition including the acidic pH of about 5. Furthermore, P2X receptors, ligand gated ion channels of the danger signal ATP, are expressed in the limiting LB membrane. They play a role in boosting surfactant secretion and fluid clearance. In this review, we discuss the functions of these transporting pathways of the LB, including possible roles in disease and as therapeutic targets, including viral infections such as SARS-CoV-2.
Topics: COVID-19; Humans; Ion Channels; Lamellar Bodies; Lung; Membrane Transport Proteins; Organelles; Pulmonary Alveoli; Pulmonary Surfactants; SARS-CoV-2
PubMed: 35011607
DOI: 10.3390/cells11010045 -
Obstetrics and Gynecology Feb 2001Lamellar bodies, concentrically layered "packages" of phospholipid that represent the storage form of surfactant, can be counted in the platelet channel of most... (Review)
Review
Lamellar bodies, concentrically layered "packages" of phospholipid that represent the storage form of surfactant, can be counted in the platelet channel of most electronic cell counters. The lamellar body count has been used for more than a decade and performs as well as traditional phospholipid analysis as an assay for evaluating fetal lung maturity. It is preferable to phospholipid analysis because it is rapid, objective, and inexpensive and can be performed in any hospital laboratory. The current methodologies for specimen preparation vary widely among laboratories, most notably with respect to centrifugation, resulting in differences in maturity cutoffs used. Our goal was to establish a consensus regarding a standardized methodology for the lamellar body count. Institutions that previously had published their results with lamellar body counts were invited to contribute. The consensus of the four participating institutions includes the following: centrifugation is not a necessary step and should be abandoned, maturity is suggested by a count of 50,000/microL or greater, and immaturity is suggested by a count of 15,000/microL or lower. As the lamellar body count gains wider acceptance as a primary assay for assessing fetal lung maturity, the test must be performed uniformly and accurately, given the implications of acting on a falsely negative test resulting from improper methodology.
Topics: Amniotic Fluid; Female; Fetal Organ Maturity; Humans; Inclusion Bodies; Infant, Newborn; Lung; Phospholipids; Predictive Value of Tests; Pregnancy; Reference Values; Specimen Handling
PubMed: 11165603
DOI: 10.1016/s0029-7844(00)01134-0 -
American Journal of Clinical Dermatology 2003Ceramides are the major lipid constituent of lamellar sheets present in the intercellular spaces of the stratum corneum. These lamellar sheets are thought to provide the... (Review)
Review
Ceramides are the major lipid constituent of lamellar sheets present in the intercellular spaces of the stratum corneum. These lamellar sheets are thought to provide the barrier property of the epidermis. It is generally accepted that the intercellular lipid domain is composed of approximately equimolar concentrations of free fatty acids, cholesterol, and ceramides. Ceramides are a structurally heterogeneous and complex group of sphingolipids containing derivatives of sphingosine bases in amide linkage with a variety of fatty acids. Differences in chain length, type and extent of hydroxylation, saturation etc. are responsible for the heterogeneity of the epidermal sphingolipids. It is well known that ceramides play an essential role in structuring and maintaining the water permeability barrier function of the skin. In conjunction with the other stratum corneum lipids, they form ordered structures. An essential factor is the physical state of the lipid chains in the nonpolar regions of the bilayers. The stratum corneum intercellular lipid lamellae, the aliphatic chains in the ceramides and the fatty acids are mostly straight long-chain saturated compounds with a high melting point and a small polar head group. This means that at physiological temperatures, the lipid chains are mostly in a solid crystalline or gel state, which exhibits low lateral diffusional properties and is less permeable than the state of liquid crystalline membranes, which are present at higher temperatures. The link between skin disorders and changes in barrier lipid composition, especially in ceramides, is difficult to prove because of the many variables involved. However, most skin disorders that have a diminished barrier function present a decrease in total ceramide content with some differences in the ceramide pattern. Formulations containing lipids identical to those in skin and, in particular, some ceramide supplementation could improve disturbed skin conditions. Incomplete lipid mixtures yield abnormal lamellar body contents, and disorder intercellular lamellae, whereas complete lipid mixtures result in normal lamellar bodies and intercellular bilayers. The utilization of physiological lipids according to these parameters have potential as new forms of topical therapy for dermatoses. An alternative strategy to improving barrier function by topical application of the various mature lipid species is to enhance the natural lipid-synthetic capability of the epidermis through the topical delivery of lipid precursors.
Topics: Animals; Ceramides; Drug Therapy, Combination; Epidermis; Humans; Skin Diseases; Skin Physiological Phenomena
PubMed: 12553851
DOI: 10.2165/00128071-200304020-00004 -
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 -
European Journal of Obstetrics,... Jun 2022There is evidence indicating that the risk of respiratory distress syndrome is reduced in preterm neonates exposed to intra-amniotic infection and/or inflammation. We...
OBJECTIVE
There is evidence indicating that the risk of respiratory distress syndrome is reduced in preterm neonates exposed to intra-amniotic infection and/or inflammation. We hypothesised that foetal lung maturation promoted by intra-amniotic infection and/or inflammation results in elevated lamellar body count (LBC) in amniotic fluid (AF). This study aimed to determine the relationship between LBC in AF and intra-amniotic infection and/or inflammation in patients with threatened preterm birth.
STUDY DESIGN
This was a retrospective cohort study of patients with threatened preterm birth. A total of 104 consecutive pregnant women underwent amniocentesis in the early preterm period [gestational age < 34 weeks] to evaluate intra-amniotic infection and/or inflammation and foetal lung maturity. Intra-amniotic infection was confirmed by positive AF culture results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma. Intra-amniotic inflammation was defined as a positive AF matrix metalloproteinase-8 rapid test. Outcomes of the study population were compared according to LBC in AF using a cut-off of 15,000/mm.
RESULTS
The rates of elevated LBC and intra-amniotic infection and/or inflammation were 23% (24/104) and 52% (54/104), respectively. The median LBC was significantly higher in patients with intra-amniotic infection and/or inflammation than in those without [median LBC, 9,000/mm (interquartile range, IQR: 3,000-39,000) vs. 3,000/mm (IQR: 2,750-5,000), p < 0.001]. Intra-amniotic infection and/or inflammation was observed in 96% (23/24) of patients with elevated LBC and 39% (31/80) of patients without elevated LBC (p < 0.001). On multivariable analysis, the presence of intra-amniotic infection and/or inflammation was significantly associated with elevated LBC with an odds ratio (OR) of 66.0 [95% confidence interval (CI) 6.6-664.4, p < 0.001], even after accounting for gestational age at amniocentesis being a significantly related factor for predicting elevated LBC with an OR of 1.5 (95% CI 1.1-2.0, p = 0.004).
CONCLUSION
LBC elevation was independently associated with the presence of intra-amniotic infection and/or inflammation in women with early threatened preterm birth (gestational age < 34 weeks). This finding may support the view that an intra-amniotic inflammatory response promotes foetal lung maturation that can be detected by elevated LBC in AF.
Topics: Amniocentesis; Amniotic Fluid; Biomarkers; Chorioamnionitis; Female; Gestational Age; Humans; Infant; Infant, Newborn; Inflammation; Lamellar Bodies; Lung; Pregnancy; Premature Birth; Retrospective Studies
PubMed: 35504118
DOI: 10.1016/j.ejogrb.2022.04.017 -
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 -
The Journal of Allergy and Clinical... Oct 2014I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and... (Review)
Review
I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in patients with atopic dermatitis (AD). Although best known are mutations in filaggrin (FLG), mutations in other member of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg-2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by TMEM79 and regulates the assembly of lamellar bodies; SPINK5, which encodes the serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1; and the fatty acid transporter fatty acid transport protein 4 have all been linked to AD. Yet these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function, such as psychological stress, low ambient humidity, or high-pH surfactants, often are required to trigger disease. T(H)2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes, and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the lamellar body secretory system, producing abnormalities in lipid composition, secretion, and/or extracellular lamellar membrane organization, as well as antimicrobial defense. Finally, I briefly review therapeutic options that address this new pathogenic paradigm.
Topics: Animals; Bodily Secretions; Dermatitis, Atopic; Fatty Acid Transport Proteins; Filaggrin Proteins; Gene-Environment Interaction; Humans; Immunity, Innate; Inclusion Bodies; Intermediate Filament Proteins; Lipid Metabolism; Membrane Proteins; Proteinase Inhibitory Proteins, Secretory; Proteolysis; Serine Peptidase Inhibitor Kazal-Type 5; Skin
PubMed: 25131691
DOI: 10.1016/j.jaci.2014.05.048 -
The Journal of Investigative Dermatology Mar 1992Abundant evidence points to an important role for epidermal lamellar body secretion in permeability-barrier maintenance. However, the response of the lamellar body...
Abundant evidence points to an important role for epidermal lamellar body secretion in permeability-barrier maintenance. However, the response of the lamellar body secretory system to barrier disruption has not been examined. Hence, we examined the lamellar body secretory response at various points after acetone-induced barrier abrogation in hairless mice in air-exposed animals and those occluded with impermeable versus vapor-permeable membranes. Tape-stripped animals served as a control for chemical toxicity. Barrier perturbation with either acetone or tape stripping was followed by rapid secretion of lamellar body contents from the uppermost granular cell layer, leaving the cytosol largely devoid of lamellar bodies. The newly secreted lamellar body contents comprised pleated sheets (not "discs," as previously thought), which unfurled in the intercellular spaces at the granular-cornified cell interface. At this time (15-30 min), the basic unit structure of the lamellar bilayers in the mid-to-upper stratum corneum appeared disorganized and interspersed with large lacunae, reflecting solvent extraction. Nascent lamellar bodies began to reappear in the granular cell cytosol by 30 min and by 360 min the cells displayed a full complement of normal-appearing lamellar bodies. Between 60 and 360 min, the density of lamellar body sheets at the granular-cornified cell interface increased, whereas the membrane bilayers of the outer stratum corneum remained disorganized. New lamellar bilayer units first appeared in the lower stratum corneum between 60 and 180 min, as a result of the transformation of secreted lamellar body sheets and over time these lamellae appeared at more apical locations. Occlusion with a water vapor-impermeable but not a vapor-permeable membrane resulted in a) decreased quantities of lamellar bodies and lamellar body-derived intercellular products; b) formation of lamellar bodies with abnormal internal contents; c) inhibition of lamellar body secretion; and d) inhibition of transformation of lamellar body-derived sheets into lamellar bilayer units. These results demonstrate the central role of the lamellar body-secretory system in barrier repair and homeostasis.
Topics: Acetone; Animals; Epidermis; Mice; Mice, Hairless; Permeability
PubMed: 1545137
DOI: 10.1111/1523-1747.ep12497866 -
Toxicology and Applied Pharmacology Oct 2020Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered...
Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.
Topics: Animals; Apoptosis; Betacoronavirus; COVID-19; Cell Line; Cell Survival; Coronavirus Infections; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred ICR; Pandemics; Pneumonia, Viral; Quaternary Ammonium Compounds; SARS-CoV-2
PubMed: 32763356
DOI: 10.1016/j.taap.2020.115182