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Cell and Tissue Research Mar 2017The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing... (Review)
Review
The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.
Topics: Animals; Diffusion; Gases; Humans; Lung
PubMed: 27981379
DOI: 10.1007/s00441-016-2541-4 -
Chest Aug 2017Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair... (Review)
Review
Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair as the gold standard for treatment, albeit it is a solution with limited success. In patients who have recently undergone thoracic surgery or in whom surgery would be contraindicated based on the severity of illness, there has been a lack of treatment options. This review describes a brief history of treatment guidelines for PALs. In the past 20 years, newer and less invasive treatment options have been developed. Aside from supportive care, the literature includes anecdotal successful reports using fibrin sealants, ethanol injection, metal coils, and Watanabe spigots. More recently, larger studies have demonstrated success with chemical pleurodesis, autologous blood patch pleurodesis, and endobronchial valves. This manuscript describes these treatment options in detail, including postprocedural adverse events. Further research, including randomized controlled trials with comparison of these options, are needed, as is long-term follow-up for these interventions.
Topics: Air; Chest Tubes; Chronic Disease; Female; Humans; Lung Diseases; Male; Pleural Diseases; Pleurodesis; Pneumothorax; Practice Guidelines as Topic; Respiratory Tract Fistula; Risk Factors; Sex Factors
PubMed: 28267436
DOI: 10.1016/j.chest.2017.02.020 -
ALTEX 2018The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an...
The air-blood barrier is mainly composed of alveolar epithelial cells and macrophages. Whereas the epithelium acts as a diffusional barrier, macrophages represent an immunological barrier, in particular for larger molecules and nanoparticles. This paper describes a new co-culture of human cell lines representing both cell types. Acquiring, culturing and maintaining primary alveolar epithelial cells presents significant logistical and technical difficulties. The recently established human alveolar epithelial lentivirus immortalized cell line, hAELVi, when grown on permeable filters, form monolayers with high functional and morphological resemblance to alveolar type I cells. To model alveolar macrophages, the human cell line THP-1 was seeded on pre-formed hAELVi monolayers. The co-culture was characterized regarding cellular morphology, viability and barrier function. Macrophages were homogenously distributed on the epithelium and could be kept in co-culture for up to 7 days. Transmission electron microscopy showed loose contact between THP-1 and hAELVi cells. When grown at air liquid interface, both cells were covered with extracellular matrix-like structure, which was absent in THP-1 mono culture. In co-culture with macrophages, hAELVi cells displayed similar, sometimes even higher, trans-epithelial electrical resistance than in mono-cultures. When exposed to silver and starch NPs, hAELVi mono-cultures were more tolerant to the particles than THP-1 mono-cultures. The viability in the co-culture was similar to that of hAELVi monocultures. Transport studies with sodium fluorescein in presence/absence of EDTA proved that the co culture acts as functional diffusion barrier. These data demonstrate that hAELVi-/THP-1 co-cultures represent a promising model for safety and permeability studies of inhaled chemicals, drugs and nanoparticles.
Topics: Alveolar Epithelial Cells; Blood-Air Barrier; Cell Line; Coculture Techniques; Humans; Macrophages; Permeability
PubMed: 29169185
DOI: 10.14573/altex.1607191 -
Comprehensive Physiology Mar 2016Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to... (Review)
Review
Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints.
Topics: Adaptation, Physiological; Animals; Humans; Lung; Pulmonary Gas Exchange
PubMed: 27065169
DOI: 10.1002/cphy.c150028 -
Cell Oct 2020During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber...
During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened. However, this would translate to omnipresent persistent inflammation. Developing in vivo real-time intravital imaging of alveoli revealed AMs crawling in and between alveoli using the pores of Kohn. Importantly, these macrophages sensed, chemotaxed, and, with high efficiency, phagocytosed inhaled bacterial pathogens such as P. aeruginosa and S. aureus, cloaking the bacteria from neutrophils. Impairing AM chemotaxis toward bacteria induced superfluous neutrophil recruitment, leading to inappropriate inflammation and injury. In a disease context, influenza A virus infection impaired AM crawling via the type II interferon signaling pathway, and this greatly increased secondary bacterial co-infection.
Topics: Animals; Bacteria; Female; Homeostasis; Humans; Lung; Macrophages; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Neutrophils; Phagocytosis; Pseudomonas aeruginosa; Pulmonary Alveoli; Signal Transduction; Staphylococcus aureus
PubMed: 32888431
DOI: 10.1016/j.cell.2020.08.020 -
Frontiers in Immunology 2020The main function of the lung is to perform gas exchange while maintaining lung homeostasis despite environmental pathogenic and non-pathogenic elements contained in... (Review)
Review
The main function of the lung is to perform gas exchange while maintaining lung homeostasis despite environmental pathogenic and non-pathogenic elements contained in inhaled air. Resident cells must keep lung homeostasis and eliminate pathogens by inducing protective immune response and silently remove innocuous particles. Which lung cell type is crucial for this function is still subject to debate, with reports favoring either alveolar macrophages (AMs) or lung epithelial cells (ECs) including airway and alveolar ECs. AMs are the main immune cells in the lung in steady-state and their function is mainly to dampen inflammatory responses. In addition, they phagocytose inhaled particles and apoptotic cells and can initiate and resolve inflammatory responses to pathogens. Although AMs release a plethora of mediators that modulate immune responses, ECs also play an essential role as they are more than just a physical barrier. They produce anti-microbial peptides and can secrete a variety of mediators that can modulate immune responses and AM functions. Furthermore, ECs can maintain AMs in a quiescent state by expressing anti-inflammatory membrane proteins such as CD200. Thus, AMs and ECs are both very important to maintain lung homeostasis and have to coordinate their action to protect the organism against infection. Thus, AMs and lung ECs communicate with each other using different mechanisms including mediators, membrane glycoproteins and their receptors, gap junction channels, and extracellular vesicles. This review will revisit characteristics and functions of AMs and lung ECs as well as different communication mechanisms these cells utilize to maintain lung immune balance and response to pathogens. A better understanding of the cross-talk between AMs and lung ECs may help develop new therapeutic strategies for lung pathogenesis.
Topics: Alveolar Epithelial Cells; Animals; Cell Communication; Homeostasis; Humans; Lung; Macrophages, Alveolar
PubMed: 33178214
DOI: 10.3389/fimmu.2020.583042 -
European Journal of Pharmaceutics and... Mar 2023The intranasal route has been receiving greater attention from the scientific community not only for systemic drug delivery but also for the treatment of pulmonary and... (Review)
Review
The intranasal route has been receiving greater attention from the scientific community not only for systemic drug delivery but also for the treatment of pulmonary and neurological diseases. Along with it, drug transport and permeability studies across the nasal mucosa have exponentially increased. Nevertheless, the translation of data from in vitro cell lines to in vivo studies is not always reliable, due to the difficulty in generating an in vitro model that resembles respiratory human physiology. Among all currently available methodologies, the air-liquid interface (ALI) method is advantageous to promote cell differentiation and optimize the morphological and histological characteristics of airway epithelium cells. Cells grown under ALI conditions, in alternative to submerged conditions, appear to provide relevant input for inhalation and pulmonary toxicology and complement in vivo experiments. Different methodologies and a variety of materials have been used to induce ALI conditions in primary cells and numerous cell lines. Until this day, with only exploratory results, no consensus has been reached regarding the validation of the ALI method, hampering data comparison. The present review describes the most adequate cell models of airway epithelium and how these models are differently affected by ALI conditions. It includes the evaluation of cellular features before and after ALI, and the application of the method in primary cell cultures, commercial 3D primary cells, cell lines and stem-cell derived models. A variety of these models have been recently applied for pharmacological studies against severe acute respiratory syndrome-coronavirus(-2) SARS-CoV(-2), namely primary cultures with alveolar type II epithelium cells and organotypic 3D models. The herein compiled data suggest that ALI conditions must be optimized bearing in mind the type of cells (nasal, bronchial, alveolar), their origin and the objective of the study.
Topics: Humans; Respiratory Mucosa; Cell Culture Techniques; Cell Line; Lung; Nasal Mucosa; Epithelial Cells
PubMed: 36696943
DOI: 10.1016/j.ejpb.2023.01.013