Surfactant protein B

Last updated
SFTPB
PDB 1dfw EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SFTPB , PSP-B, SFTB3, SFTP3, SMDP1, SP-B, surfactant protein B, Surfactant protein B
External IDs OMIM: 178640 MGI: 109516 HomoloGene: 456 GeneCards: SFTPB
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000542
NM_198843
NM_001367281

NM_001282071
NM_147779

RefSeq (protein)

NP_000533
NP_942140
NP_001354210

NP_001269000
NP_680088

Location (UCSC) Chr 2: 85.66 – 85.67 Mb Chr 6: 72.28 – 72.29 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Surfactant protein B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. [5] It rearranges lipid molecules in the fluid lining the lung so that tiny air sacs in the lung, called alveoli, can more easily inflate. [6]

Gene

SP-B is encoded by SFTPB, a single, 11425 nucleotide long gene on chromosome 2. [7] Mutations in this gene are the basis for several of the lung conditions mentioned above. Both frameshift mutations and several single nucleotide polymorphisms (SNPs) have been found correlated to a variety of lung conditions. A frame shift mutation responsible for congenital alveolar proteinosis (CAP) was identified by Kattan et al. [8] Many SNP's have been identified in relation to lung conditions. They have been correlated to severe influenza, neonatal respiratory distress syndrome, mechanical ventilation necessity, and more. [9]

Protein

Surfactant protein B (SP-B) is a small protein, weighing about 8 kDa. [10] Proteins are composed of building blocks called amino acids, and SP-B is composed of 79 of them (Valine, alanine, phenylalanine, leucine, isoleucine, and tryptophan being found in the highest levels). Nine of these carry with them a positive charge, and two carry a negative charge, leaving a protein with a net (total) charge of +7. [5] In the body, two molecules of SP-B stick together and form what is called a homodimer. [11] These are found embedded into membranes and other lipid structures, SP-B is a highly hydrophobic, avoiding contact with water.

SP-B is the mature form of a large precursor protein called proSP-B. Synthesized in the endoplasmic reticulum of type II pneumocytes, proSP-B weighs approximately 40 kDa and is cut down to the size of mature SP-B in the golgi apparatus through a process called post-translational modification. [5] ProSP-B is also created in another type of lung cell called a Club cell, but these cells are unable to edit proSP-B into SP-B. [11]

SP-B is a saposin-like protein, which is a group of related proteins known particularly for binding to membranes with negative charges and facilitating either the fusion or lysis (breaking) of the membrane. More well known proteins in this family include saposin-C, NK-lysin, and amoebopore. [6]

Function

SP-B plays a critical role in the functioning of healthy lungs, and its absence inevitably leads to lung conditions, most common of which being acute respiratory distress syndrome (ARDS). Because of this, SP-B's function has been well researched, and has been found to exist in three parts. Beyond these three functions, it is worth noting that SP-B is also thought to have some anti-inflammatory function, though it is not well defined. [12]

Indirect surface tension reduction

The surface tension at the border between the fluid lining and the inhaled gas (gas/fluid interface) in alveoli determines the motion of the alveoli as a whole. According to Lapace's Law, high surface tension in the gas/fluid interface of alveoli prevents the alveoli from inflating, which causes lung collapse. [13] lipid arrangement in the fluid lining of alveoli is the primary determining factor of this surface tension since the lipids form a thin film (monolayer) on the surface of the fluid lining at the gas/fluid interface. Different lipids allow for different ranges of motion and can be compacted different.[ citation needed ]

SP-B plays a role in this by selected certain lipids and inserting them into the gas/fluid interface. The lipid shown to be most needed on this surface (Dipalmitoylphosphatidylcholine) does not easily move to the gas/fluid interface, but SP-B helps ease and speed up this process. [14]

SP-B also indirectly reduces surface tension by organizing the lipids underneath the surface of the gas/fluid interface in structures called tubular myelin. [5] Effectively, SP-B cuts and pastes pieces of the lipid bilayers to form the three dimensional structure of the tubular myelin. This structure is the support and lipid source for the gas/fluid interface, where surface tension is a critical factor in lung function.

Direct surface tension reduction

Beyond arranging lipids in a way that reduces surface tension, SP-B actually directly interferes with attractive forces between water molecules. [12] This disruption in the cohesion of water minimizes further the surface tension at the gas/fluid interface.

Formation of lamellar bodies

Lamellar bodies are groups of lipids and protein that are structurally similar to tubular myelin, but are found inside instead of outside the type II pneumocytes. Similarly to its function in organizing tubular myelin, SP-B arranges lipids into the lamellar body structure. [6] Basically, SP-B plays a role in the organogenesis (formation of structure) of lamellar bodies. The lamellar bodies are then secreted into the fluid lining the interior of alveoli, and become tubular myelin. This role is critical for making pulmonary surfactant (see below)

SP-B Deficiencies and Issues

Acute respiratory distress syndrome, respiratory syncytial virus infection, familial lung disease, and pneumocystis infection are examples of deficiencies in and issues with SP-B that are correlated with lung issues. [15]

Because so many lung conditions are associated with issues around SP-B, synthetic replacements have been researched, created, and manufactured. It has been shown that 21 amino acid long peptides with positive charge and intermittent hydrophobic regions mimicking SP-B can minimize surface tension at the gas/fluid interface, and surfactant replacements for surfactant deficient patients has been used to save lives. [16] [17]

Once lung distress has occurred, SP-B has been shown to be effective as a biomarker in the blood stream. [10] Higher levels of SP-B indicate some kind of lung distress, and can even indicate if the patient is currently a smoker. [18] This may be useful in the future to predict atherosclerosis, a solidifying of vascular tissue that has negative effects on the heart.

Context in surfactant

SP-B is a critical protein for lung function, and is found in the context of pulmonary surfactant. Understanding surfactant is important to gaining a full understanding of SP-B. Surfactant is a mixture of lipids and proteins that coats the inside of alveoli and is essential for life due to its key role in preventing alveolar collapse at low lung volumes. [19] [7] In the absence of surfactant, the surface tension at the gas/fluid interface prevents inhalation at standard pressure, but surfactant minimizes surface tension to values near zero and allows for normal breathing. [20] It is also known to have a role in both the immune response and inflammation control.

Surfactant deficiency is a common cause of respiratory disease. Respiratory distress syndrome (RDS) is a particularly well-known instance of surfactant deficiency because it has a high mortality rate among preterm babies, a variety of other conditions are related to surfactant levels and composition. [21]

Surfactant is composed of primarily lipids (90% by weight), and proteins make up only the remaining 10%. The following two sections will address the lipid and protein components respectively.

Surfactant lipids

Lipids are a broad category of mid-sized molecules that are hydrophobic or amphipathic. In surfactant, two subcategories of lipids are relevant: phospholipids and sterols. Sterols are represented by cholesterol, which has an important role in the overall structure and motion of the lipids as a whole, but is vastly outnumbered by the phospholipids in surfactant.

DPPC (dipalmitoylphosphatidylcholine), as mentioned above, is a lipid with very useful stabilizing and compacting attributes. SP-B works primarily with this lipid, and moves it to the gas/fluid interface where it minimized surface tension. [6] Essentially, DPPC is so important for lung function because it can shrink or expand to fit the space necessary, and a continually shrinking and expanding lung requires components like this.

Other lipids found commonly in surfactant include phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidylserine (PS).

Surfactant proteins

SP-B is one of four proteins commonly found in surfactant, the other three being surfactant protein A (SP-A), surfactant protein C (SP-C), and surfactant protein D (SP-D). [7] These four are highly interconnected in their functions in surfactant. For example, though the mechanism is not yet understood, SP-B functions in the post-translational modification of SP-C, and mature SP-C is not formed without SP-B. [5]

SP-C assists in the functions of SP-B, and is most similar to SP-B of the three other surfactant proteins. It is smaller, only 35 amino acids long, and is found embedded in lipid structures much like SP-B. [5]

SP-A and SP-D, known together as collectins, are more distinct from SP-B than SP-C. They are hydrophilic, so they are found in the solution, and function in immune response instead of lipid arrangement and surface tension reduction. [20] [19] SP-A is actually a name for two very similar proteins, SP-A1 and SP-A2.

Along with SP-A, B, C, and D, blood plasma proteins are found in very small quantities in surfactant as well.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Meconium aspiration syndrome</span> Medical condition affecting newborn infants

Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.

<span class="mw-page-title-main">Lung</span> Primary organ of the respiratory system

The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of the heart. Their function in the respiratory system is to extract oxygen from the air and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. The pleurae, which are thin, smooth, and moist, serve to reduce friction between the lungs and chest wall during breathing, allowing for smooth and effortless movements of the lungs.

<span class="mw-page-title-main">Respiratory system</span> Biological system in animals and plants for gas exchange

The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies greatly, depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs; in mammals and reptiles these are called alveoli, and in birds they are known as atria. These microscopic air sacs have a very rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi. These enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds the bronchioles are termed parabronchi. It is the bronchioles, or parabronchi that generally open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration.

<span class="mw-page-title-main">Pulmonary alveolus</span> Hollow cavity found in the lungs

A pulmonary alveolus, also known as an air sac or air space, is one of millions of hollow, distensible cup-shaped cavities in the lungs where pulmonary gas exchange takes place. Oxygen is exchanged for carbon dioxide at the blood–air barrier between the alveolar air and the pulmonary capillary. Alveoli make up the functional tissue of the mammalian lungs known as the lung parenchyma, which takes up 90 percent of the total lung volume.

<span class="mw-page-title-main">Surfactant</span> Substance that lowers the surface tension between a liquid and another material

Surfactants are chemical compounds that decrease the surface tension or interfacial tension between two liquids, a liquid and a gas, or a liquid and a solid. Surfactants may function as emulsifiers, wetting agents, detergents, foaming agents, or dispersants. The word "surfactant" is a blend of surface-active agent, coined c.  1950.

<span class="mw-page-title-main">Infant respiratory distress syndrome</span> Human disease affecting newborns

Infantile respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.

<span class="mw-page-title-main">Pulmonary surfactant</span>

Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-water interface of alveoli, with hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.

<span class="mw-page-title-main">Pulmonary hemorrhage</span> Medical condition

Pulmonary hemorrhage is an acute bleeding from the lung, from the upper respiratory tract and the trachea, and the pulmonary alveoli. When evident clinically, the condition is usually massive. The onset of pulmonary hemorrhage is characterized by a cough productive of blood (hemoptysis) and worsening of oxygenation leading to cyanosis. Treatment should be immediate and should include tracheal suction, oxygen, positive pressure ventilation, and correction of underlying abnormalities such as disorders of coagulation. A blood transfusion may be necessary.

<span class="mw-page-title-main">Dipalmitoylphosphatidylcholine</span> Chemical compound

Dipalmitoylphosphatidylcholine (DPPC) is a phospholipid (and a lecithin) consisting of two C16 palmitic acid groups attached to a phosphatidylcholine head-group.

<span class="mw-page-title-main">Lamellar bodies</span> Secretory organelles

In cell biology, lamellar bodies are secretory organelles found in type II alveolar cells in the lungs, and in keratinocytes in the skin. They are oblong structures, appearing about 300-400 nm in width and 100-150 nm in length in transmission electron microscopy images. Lamellar bodies in the alveoli of the lungs fuse with the cell membrane and release pulmonary surfactant into the extracellular space.

<span class="mw-page-title-main">Surfactant protein D</span> Protein-coding gene in the species Homo sapiens

Surfactant protein D, also known as SP-D, is a lung surfactant protein part of the collagenous family of proteins called collectin. In humans, SP-D is encoded by the SFTPD gene and is part of the innate immune system. Each SP-D subunit is composed of an N-terminal domain, a collagenous region, a nucleating neck region, and a C-terminal lectin domain. Three of these subunits assemble to form a homotrimer, which further assemble into a tetrameric complex.

Surfactant protein A is an innate immune system collectin. It is water-soluble and has collagen-like domains similar to SP-D. It is part of the innate immune system and is used to opsonize bacterial cells in the alveoli marking them for phagocytosis by alveolar macrophages. SP-A may also play a role in negative feedback limiting the secretion of pulmonary surfactant. SP-A is not required for pulmonary surfactant to function but does confer immune effects to the organism.

<span class="mw-page-title-main">Surfactant protein C</span> Protein-coding gene in the species Homo sapiens

Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the SFTPC gene.

<span class="mw-page-title-main">Surfactant protein A1</span> Protein-coding gene in the species Homo sapiens

Surfactant protein A1(SP-A1), also known as Pulmonary surfactant-associated protein A1(PSP-A) is a protein that in humans is encoded by the SFTPA1 gene.

<span class="mw-page-title-main">Surfactant protein A2</span> Protein-coding gene in the species Homo sapiens

Surfactant protein A2(SP-A2), also known as Pulmonary surfactant-associated protein A2(PSP-A2) is a protein that in humans is encoded by the SFTPA2 gene.

<span class="mw-page-title-main">Lecithin–sphingomyelin ratio</span>

The lecithin–sphingomyelin ratio is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs. This is especially important for premature babies trying to expand their lungs after birth. Surfactant is a mixture of lipids, proteins, and glycoproteins, lecithin and sphingomyelin being two of them. Lecithin makes the surfactant mixture more effective.

<span class="mw-page-title-main">Diffuse alveolar damage</span> Medical condition

Diffuse alveolar damage (DAD) is a histologic term used to describe specific changes that occur to the structure of the lungs during injury or disease. Most often DAD is described in association with the early stages of acute respiratory distress syndrome (ARDS). It is important to note that DAD can be seen in situations other than ARDS (such as acute interstitial pneumonia) and that ARDS can occur without DAD.

Poractant alfa is a pulmonary surfactant sold under the brand name Curosurf by Chiesi Farmaceutici. Poractant alfa is an extract of natural porcine lung surfactant. As with other surfactants, marked improvement on oxygenation may occur within minutes of the administration of poractant alfa. The new generic form of surfactant is Varasurf developed in PersisGen Co. and commercialized by ArnaGen Pharmad. It has fully comparable quality profile with Curosurf.

Surfactant metabolism dysfunction is a condition where pulmonary surfactant is insufficient for adequate respiration. Surface tension at the liquid-air interphase in the alveoli makes the air sacs prone to collapsing post expiration. This is due to the fact that water molecules in the liquid-air surface of alveoli are more attracted to one another than they are to molecules in the air. For sphere-like structures like alveoli, water molecules line the inner walls of the air sacs and stick tightly together through hydrogen bonds. These intermolecular forces put great restraint on the inner walls of the air sac, tighten the surface all together, and unyielding to stretch for inhalation. Thus, without something to alleviate this surface tension, alveoli can collapse and cannot be filled up again. Surfactant is essential mixture that is released into the air-facing surface of inner walls of air sacs to lessen the strength of surface tension. This mixture inserts itself among water molecules and breaks up hydrogen bonds that hold the tension. Multiple lung diseases, like ISD or RDS, in newborns and late-onsets cases have been linked to dysfunction of surfactant metabolism.

Ka Yee Christina Lee is a Professor of Chemistry and the Provost at the University of Chicago, where she succeeded Daniel Diermeier on February 1, 2020. She works on membrane biophysics, including protein–lipid interactions, Alzheimer's disease and respiratory distress syndrome. She is a Fellow of the American Institute for Medical and Biological Engineering and American Physical Society.

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