Review

Authors: M Kolomaznik, Z Nova, A Calkovska...

The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.

Topics: Acute Lung Injury; Animals; Biological Products; Humans; Lipopolysaccharides; Lung; Phospholipids; Pulmonary Surfactants; Swine

PubMed: 28937231
DOI: 10.33549/physiolres.933672

Review

Authors: Alberto Hidalgo, Antonio Cruz, Jesús Pérez-Gil...

Pulmonary surfactant is a membrane-based lipid-protein system essential for the process of breathing, which coats and stabilizes the whole respiratory surface and possesses exceptional biophysical properties. It constitutes the first barrier against the entry of pathogens and harmful particles in the alveolar region, extended through the lungs, but on the other hand, it can offer novel possibilities as a shuttle for the delivery of drugs and nanocarriers. The advances in nanotechnology are opening the doors to new diagnostic and therapeutic avenues, which are not accessible by means of the current approaches. In this context, the pulmonary route is called to become a powerful way of entry for innovative treatments based on nanotechnology. In this review, the anatomy of the respiratory system and its properties for drug entry are first revisited, as well as some current strategies that use the respiratory route for both local and peripheral action. Then, a brief overview is presented on what pulmonary surfactant is, how it works and why it could be used as a drug delivery vehicle. Finally, the review is closed with a description of the development of nanocarriers in the lung context and their interaction with endogenous and clinical pulmonary surfactants. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Topics: Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Nanomedicine; Nanoparticles; Particle Size; Pulmonary Surfactants

PubMed: 28450046
DOI: 10.1016/j.bbamem.2017.04.019

Review

Authors: S A Rooney

Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.

Topics: Adrenergic beta-Agonists; Animals; Cyclic AMP; Diabetes Mellitus; Estrogens; Female; Fetus; Glucocorticoids; Glycogen; Humans; Lipids; Lung; Parasympathomimetics; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylglycerols; Pregnancy; Prolactin; Prostaglandins; Pulmonary Surfactants; Subcellular Fractions; Thyrotropin-Releasing Hormone

PubMed: 6145585
DOI: 10.1289/ehp.8455205

Review

Authors: Feifei Wang, Jifang Liu, Hongbo Zeng...

Particulate matter (PM), which is the primary contributor to air pollution, has become a pervasive global health threat. When PM enters into a respiratory tract, the first body tissues to be directly exposed are the cells of respiratory tissues and pulmonary surfactant. Pulmonary surfactant is a pivotal component to modulate surface tension of alveoli during respiration. Many studies have proved that PM would interact with pulmonary surfactant to affect the alveolar activity, and meanwhile, pulmonary surfactant would be adsorbed to the surface of PM to change the toxic effect of PM. This review focuses on recent studies of the interactions between micro/nanoparticles (synthesized and environmental particles) and pulmonary surfactant (natural surfactant and its models), as well as the health effects caused by PM through a few significant aspects, such as surface properties of PM, including size, surface charge, hydrophobicity, shape, chemical nature, etc. Moreover, in vitro and in vivo studies have shown that PM leads to oxidative stress, inflammatory response, fibrosis, and cancerization in living bodies. By providing a comprehensive picture of PM-surfactant interaction, this review will benefit both researchers for further studies and policy-makers for setting up more appropriate regulations to reduce the adverse effects of PM on public health.

Topics: Animals; Health; Humans; Nanoparticles; Particulate Matter; Pulmonary Surfactants

PubMed: 32871405
DOI: 10.1016/j.cis.2020.102244

Review

Authors: Mercedes Echaide, Chiara Autilio, Raquel Arroyo...

Pulmonary surfactant is a complex of lipids and proteins assembled and secreted by the alveolar epithelium into the thin layer of fluid coating the respiratory surface of lungs. There, surfactant forms interfacial films at the air-water interface, reducing dramatically surface tension and thus stabilizing the air-exposed interface to prevent alveolar collapse along respiratory mechanics. The absence or deficiency of surfactant produces severe lung pathologies. This review describes some of the most important surfactant-related pathologies, which are a cause of high morbidity and mortality in neonates and adults. The review also updates current therapeutic approaches pursuing restoration of surfactant operative films in diseased lungs, mainly through supplementation with exogenous clinical surfactant preparations. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Topics: Animals; Humans; Lung; Meconium Aspiration Syndrome; Pulmonary Surfactants; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn

PubMed: 28341439
DOI: 10.1016/j.bbamem.2017.03.015

Review

Authors: Mari Numata, Pitchaimani Kandasamy, Dennis R Voelker...

The pulmonary surfactant system of the lung is a lipid and protein complex, which regulates the biophysical properties of the alveoli to prevent lung collapse and the innate immune system in the lung. Pulmonary surfactant is a lipoprotein complex consisting of 90% phospholipids and 10% protein, by weight. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), exist at very high concentrations in the extracellular alveolar compartments. We have reported that one of the most dominant molecular species of PG, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and PI inhibit inflammatory responses induced by multiple toll-like receptors (TLR2/1, TLR3, TLR4, and TLR2/6) by interacting with subsets of multiprotein receptor components. These lipids also exert potent antiviral effects against RSV and influenza A, in vitro, by inhibiting virus binding to host cells. POPG and PI inhibit these viral infections in vivo, in multiple animal models. Especially noteworthy, these lipids markedly attenuate SARS-CoV-2 infection including its variants. These lipids are natural compounds that already exist in the lung and, thus, are less likely to cause adverse immune responses by hosts. Collectively, these data demonstrate that POPG and PI have strong potential as novel therapeutics for applications as anti-inflammatory compounds and preventatives, as treatments for broad ranges of RNA respiratory viruses.

Topics: Animals; Humans; Phospholipids; Pulmonary Surfactants; Antiviral Agents; Toll-Like Receptor 2; COVID-19; SARS-CoV-2; Lung; Anti-Inflammatory Agents; Phosphatidylglycerols

PubMed: 37144896
DOI: 10.1111/imr.13207

Review

Authors: Mari Numata, Dennis R Voelker

Pulmonary surfactant is a mixture of lipids and proteins, consisting of 90% phospholipid, and 10% protein by weight, found predominantly in pulmonary alveoli of vertebrate lungs. Two minor components of pulmonary surfactant phospholipids, phosphatidylglycerol (PG) and phosphatidylinositol (PI), are present within the alveoli at very high concentrations, and exert anti-inflammatory effects by regulating multiple Toll like receptors (TLR2/1, TLR4, and TLR2/6) by antagonizing cognate ligand-dependent activation. POPG also attenuates LPS-induced lung injury in vivo. In addition, these lipids bind directly to RSV and influenza A viruses (IAVs) and block interaction between host cells and virions, and thereby prevent viral replication in vitro. POPG and PI also inhibit RSV and IAV infection in vivo, in mice and ferrets. The lipids markedly inhibit SARS-CoV-2 infection in vitro. These findings suggest that both POPG and PI have strong potential to be applied as both prophylaxis and post-infection treatments for problematic respiratory viral infections.

Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Ferrets; Lung; Mice; Phospholipids; Pulmonary Surfactants; SARS-CoV-2; Toll-Like Receptor 2; COVID-19 Drug Treatment

PubMed: 35240310
DOI: 10.1016/j.bbalip.2022.159139

Review

Authors: Dan Li, Xianzheng Wang, Yingzhao Liao...

Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.

Topics: Humans; Lung; Pulmonary Surfactants; Respiration, Artificial; Surface-Active Agents; COVID-19 Drug Treatment

PubMed: 35592339
DOI: 10.3389/fimmu.2022.842453

Review

Authors: Maria Lisa Garavaglia, Francesca Bodega, Cristina Porta...

The alveolar epithelium is covered by a non-cellular layer consisting of an aqueous hypophase topped by pulmonary surfactant, a lipo-protein mixture with surface-active properties. Exposure to cigarette smoke (CS) affects lung physiology and is linked to the development of several diseases. The macroscopic effects of CS are determined by several types of cell and molecular dysfunction, which, among other consequences, lead to surfactant alterations. The purpose of this review is to summarize the published studies aimed at uncovering the effects of CS on both the lipid and protein constituents of surfactant, discussing the molecular mechanisms involved in surfactant homeostasis that are altered by CS. Although surfactant homeostasis has been the topic of several studies and some molecular pathways can be deduced from an analysis of the literature, it remains evident that many aspects of the mechanisms of action of CS on surfactant homeostasis deserve further investigation.

Topics: Pulmonary Surfactants; Electronic Nicotine Delivery Systems; Surface-Active Agents; Nicotiana; Lung

PubMed: 37511463
DOI: 10.3390/ijms241411702

Review

Authors: Jennifer R Glasser, Rama K Mallampalli

Pulmonary surfactant is a complex surface-active substance comprised of key phospholipids and proteins that has many essential functions. Surfactant's unique composition is integrally related to its surface-active properties, its critical role in host defense, and emerging immunomodulatory activities ascribed to surfactant lipids. Together these effector functions provide for lung stability and protection from a barrage of potentially virulent infectious pathogens.

Topics: Animals; Communicable Diseases; Humans; Immunologic Factors; Lung Diseases; Pulmonary Surfactants

PubMed: 21945366
DOI: 10.1016/j.micinf.2011.08.019