key: cord-0040020-fx1ym2fq authors: Saxena, Shweta title: Lung surfactant: The indispensable component of respiratory mechanics date: 2005 journal: nan DOI: 10.1007/bf02866749 sha: 6107c54a5410b67f84fcbd98b8a12067efd56fa8 doc_id: 40020 cord_uid: fx1ym2fq Lung surfactant, a lipo-protein complex, is a highly surface-active material found in the fluid lining the air-liquid interface of the alveolar surface. Surfactant plays a dual function of preventing alveolar collapse during breathing cycle and protection of the lungs from injuries and infections caused by foreign bodies and pathogens. Varying degrees of structure-function abnormalities of surfactant have been associated with obstructive lung diseases, respiratory infections, respiratory distress syndromes, interstitial lung diseases, pulmonary alveolar proteinosis, cardiopulmonary bypass surgery and smoking. For some pulmonary conditions, especially respiratory distress syndrome, surfactant therapy is on the horizon. Lungs differ considerably in structure, embryological origin, and function between vertebrate groups. But all lungs have a few common characteristics, v/z. they are internal, fluid lined, gas-holding structures that inflate and deflate cyclically. As a result, all lungs face potential problems related to the surface Keywords Surfactant proleins; surfac|ont phospholipids, surface activity, pulmonary diseases, surfoctant dysfunction, tension of the fluid as well as protection from the potential immunological attack from pathogens, allergens, and pollutants. To counteract these problems, pulmonary surfactant is produced in the lungs to play dual functions of maintenance of normal respiratory cycle as well as protection against immunological burdens [1] . Pulmonary surfactant is essential for normal breathing, alveolar stability and host defense system in the lungs. Basically, three very interesting biophysical properties of pulmonary surfactant underlie its physiological and immunological functions: 1) Once secreted to the alveolar spaces, surfactant adsorbs rapidly to the air-liquid interface (this happens during a newborn baby's first breath). 2) Once at the interface, surfactant films reduce surface tension to extremely low values when compressed during expiration (this means that our lungs don't collapse when we breath out). 3) Surfactant proteins recognize bacterial, fungal and viral surface oligosaccharides and thus can opsonize these pathogens. The lung surfactant evolved when vertebrates began air breathing between 320 and 420 million years ago. After the discovery of the basic functional principle of pulmonary surfactant more than 70 years ago, the pulmonary surfactant system has been intensively investigated and more than 9000 publications have revealed numerous aspects ofsurfactant synthesis, secretion, metabolism and various functions in the alveolar compartment. The human pulmonary surfactant is an array of approximately 80% phospholipids, 8% neutral lipids (cholesterol and free fatty acids) and 12% proteins, which is produced, secreted, and recycled by Type II pneumocytes [2] . The most abundant phospholipid is phosphatidylcholine (PC), especially dipalmitoylphosphatidylcholine (DPPC). DPPC is the main component of surfactant that reduces surface tension. The other lipid components of the surfactant are phosphatidylglycerol, phosphatidylinositol and cholesterol, which facilitate the adsorption of DPPC with the help of hydrophobic surfactant proteins [2] . In addition to lipids, there are four surfactant proteins (SPs) expressed by respiratory epithelial cells, designated as SP-A, SP-B, SP-C and SP-D. Out of these, SP-A and SP-D are large glycosylated water-soluble proteins and members of the calciumdependent carbohydrate-binding collectin family, which have a role in the host defence of the lung. SP-A is also important in the organization and function of the surfactant complex regulating surfactant recycling and secretion. While, SP-B and SP-C are highly hydrophobic small peptides that confer surface tension-lowering properties and are important for the adsorption and spreading of the surfactant. With the exception of SP-A, surfactant proteins are synthesized in polyribosomes, modified in the endoplasmic reticulum, golgi apparatus and multivesicular bodies and stored in lamellar bodies before secretion. Surfactant phospholipids are synthesized in the endoplasmic reticulum, transported through the golgi apparatus into multivesicular bodies and packaged into lamellar bodies. After exocytosis of lamellar bodies, surfactant phospholipids, in the presence of SP-A, SP-B and Ca ~+, are organized into a lattice structure called tubular myelin (TM), which forms a lipid-rich layer at the airliquid interface of the alveolus. Most of the extracellular surfactant is taken up by type II cells, catabolized and transported into lamellar bodies for recycling [2] (Figure 1 ). The surface tension of the alveolar air-water interface provides the retractive force opposing lung inflation. The presence of surfactant in the fluid film can lower airwater surface tensions to near zero values. This ensures that the alveolar space is open during the whole respiratory cycle preventing intra-pulmonary shunts resulting in inadequate oxygenation of the blood. Thus, the net benefit is reduced work of breathing, t Further, it also improves mucociliary transport and facilitates removal of particles and debris from the alveoli into the large airways by lowering surface tension during end-expiration [1] . Lungs reside at the interface of the body and the environment, making it especially vulnerable to enormous immunological burden from pathogens, allergens, and pollutants. To counteract the vulnerability of lungs, the protective immune mechanisms are also located locally in the lungs to facilitate clearance of pathogens and to modulate inflammatory responses. SP-A and SP-D have recently been identified as participants of host defense mechanism against infection and inflammation [3] . These are the members of collectin protein family, which have an Nterminal collagen-like region and a C-terminal lectin domain, which binds carbohydrates in a calcium dependent manner (Figure 2 ). These C-type lectin domains are arrayed with spatial orientation that confers unique carbohydrate specificities, and their preferential binding sites for nonhost oligosaccharides, such as those found on bacterial and viral surfaces [3] . The possible involvement of pulmonary surfactant in the pathophysiology of obstructive lung diseases with a predominant disturbance in the conducting airways, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis and pneumonia has only recently been addressed. Models of airway closure suggest a theoretical use of surfactant in asthma, and clinical studies have suggested that surfactant from asthmatics is functionally impaired. The main mechanism of such impairment appears to be the influx of inhibitory proteins into the airways. Also, products of inflammatory cells (including proteases and reactive oxygen and nitrogen species) and airway edema may also contribute to surfactant dysfunction. SP-A being critical for host defence against pathogens, any structure-function abnormality in this renders the CF subjects susceptible to respiratory infections. In a separate study, the BAL fluid recovered from patients with pneumonia showed reduced levels of PC, PG and alterations in fatty acid composition. In addition, amount of SP-A is also decreased and surfactant function is impaired. Mutations of surfactant protein encoding genes are associated with several multifactorial respiratory airway diseases. Allelic variations of the SP-A and SP-B genes have been shown to be important genetic determinants in individual susceptibility to respiratory distress syndrome, which is a good general model for a multifactorial pulmonary disease resulting from complex interactions between several environmental and genetic factors. Because SP-A and SP-D act directly in the clearance of common lung pathogens, the genes encoding these proteins have been implicated as candidates in a few infectious diseases, including respiratory syncytial virus (RSV) infections and tuberculosis. Investigations on pulmonary surfactant system in humans has advanced our understanding of lung physiology in health and disease, which may lead to the development of new approaches to the treatment of respiratory pathological conditions. The success of intratracheal instillation of surfactant in neonatal RDS has stimulated its potential utility in adult respiratory diseases with possible surfactant abnormalities such as ARDS, pneumonia, COPD, asthma and emphysema. Since these respiratory diseases are ofheterogenous nature and not all patients are responders to certain treatment strategies, a possible link with genetic predisposition to such diseases appears likely. Thus, it is important to study potential genetic markers, such as surfactant proteins, in order to understand these disease mechanisms clearly. Pulmonary surfactant in health and human lung diseases: state of the art Role of pulmonary surfactant components in surface film formation and dynamics Collectins and pulmonary host defense Surfactant protein-A: new insights into an old protein-Part I Surfactant protein-A: new insights into an old protein-II Surfactant protein-A levels in patients with acute respiratory distress syndrome In: Hand Book of Physiology. The Respiratory System