Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies
Specialty
Pulmonology
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.[1] Multiple lung diseases, like ISD or RDS, in newborns and late-onsets cases have been linked to dysfunction of surfactant metabolism.
Surfactant is a mixture of 90% phospholipids and 10% other proteins, produced by epithelial type II cells in the alveolar. This mixture is made and packaged into lysosomally- derived structures called lamellar bodies. Lamellar bodies are then secreted into the liquid-air interphase surface of alveolar through membrane fusion initiated by influx of Ca2+.[2] Released pulmonary surfactant acts as a protective layer to prevent alveolar from collapsing due to surface tension. Furthermore, surfactants also contains some innate immune components to defend against pulmonary infections. Surfactant is classified into two types of proteins, hydrophilic proteins that are responsible for innate immune system, and hydrophobic proteins that carry out physical functions of pulmonary surfactant.[3] Surfactant metabolism dysfunction involves mutations or malfunctions of those hydrophobic proteins that lead to ineffective surfactant layer to protect alveolus integrity.[3] SP-B and SP-C are the two hydrophobic surfactant proteins that participate in its physical functions; these proteins are encoded by SFTPB and SFTPC genes on chromosomes 2 and 8 respectively.[4] Thus, mutations on these genes produce incomplete or nonfunctioning SP-B and SP-C proteins and lead to lung diseases.
Both SP-B and SP-C are synthesized in epithelial type II cells as large precursor proteins (proSP-B and proSP-C) and subsequently cleaved by proteolytic enzymes at both amino and carboxyl termini to produce functional mature proteins.[3] proSP-B and proSP-C are first made in the endoplasmic reticulum of epithelial type II cell, they are then translocated through Golgi apparatus to multivesicular bodies for delivery to lamellar bodies. During this transition, proteolytic processing begins to cleave precursor proteins. Once multivescular body reaches the membrane of lamellar body, both membranes fuse together so that processed proteins can be transported into lamellar body, where last steps of maturation for both SP-B and SP-C occur.[4] When lamellar body is ready to be secreted, exocytosis is initiated through influx of Ca2+, and lamellar membrane fuses with plasma membrane to release surfactant phospholipid contents into the surface of the cell.[2] SP-B and SP-C are responsible to carry out adsorption of the lipid monolayer at the liquid-air interphase to prevent post expiration atelectasis. Used surfactant phospholipid materials are taken up into epithelial type II cells by pulmonary macrophages.[2]
Another important protein that contributes to outcome of surfactant metabolism dysfunction is ABCA3, a transmembrane phospholipid transporter in lamellar body. ABCA3 has two ATP binding sites in the cytoplasmic domain to power phospholipid transportation through ATP hydrolysis. ABCA3 is synthesized in endoplasmic reticulum and transported through Golgi apparatus to the membrane of lamellar body.[4] Once inserted into the membrane, ABCA3 can help deliver surfactant lipids into the lumen of lamellar body, and create tightly packed internal environment of surfactant lipids and surfactant proteins. Mutations in ABCA3 cause failure in lamellar body synthesis and result in decreased production of surfactant, along with deficiency of SP-B and SP-C.[3]
Surfactantmetabolismdysfunction is a condition where pulmonary surfactant is insufficient for adequate respiration. Surface tension at the liquid-air...
alveolar proteinosis Surfactantmetabolismdysfunction In late 1920s von Neergaard identified the function of the pulmonary surfactant in increasing the...
suggesting a chaperone activity. Mutations are associated with surfactantmetabolismdysfunction type 2. Humans and animals born lacking SP-C tend to develop...
through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. It also decreases bone formation....
for the synthesis of pulmonary surfactant, which is a mixture consisting mostly of phosphatidylcholines. The surfactant is responsible for lung elasticity...
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...
associated to cataract-microcornea syndrome. It is associated with Surfactantmetabolismdysfunction type 3. ATP-binding cassette transporter GRCh38: Ensembl release...
Surfactant protein D, also known as SP-D, is a lung surfactant protein part of the collagenous family of lectins called collectin. In humans, SP-D is encoded...
central nervous system. Other actions include contributing to pulmonary surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance...
alveoli. Surfactant reduces this danger to negligible levels, and keeps the alveoli dry. Pre-term babies who are unable to manufacture surfactant have lungs...
loss, neuropathic pain, and autonomic dysfunction (such as postural hypotension, diarrhoea, and erectile dysfunction). Loss of pain sensation predisposes...
"Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactantdysfunction". The Journal of Biological Chemistry. 289 (15): 10668–79. doi:10...
stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction. There are about 36 different types of amyloidosis, each due to a specific...
inorganic salts. Bilirubin is its major pigment. Bile acts partly as a surfactant which lowers the surface tension between either two liquids or a solid...
lung maturity is associated with how much surfactant the fetus is producing. Reduced production of surfactant indicates decreased lung maturity and is...
behaviour) in farmyard animals, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Parkinson's disease...
MBAS assay cannot distinguish between specific surfactants, however. Some examples of anionic surfactants are carboxylates, phosphates, sulfates, and sulfonates...
"Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactantdysfunction". The Journal of Biological Chemistry. 289 (15): 10668–79. doi:10...
and allows the heart to function in anaerobic metabolism without evidence of myocardial dysfunction. Cerebral integrity in Weddell seals is maintained...
correlated with lower levels of the surfactant protein indicating a relationship between surface and 14-3-3 proteins. Surfactant is an important element in the...
that are hypothesised to disrupt normal development and balance of lipid metabolism, which in some cases, can lead to obesity. Obesogens may be functionally...
mechanical ventilation remains the therapeutic mainstay for pulmonary dysfunction following acute inhalation injury. Smoke inhalation injury, either by...
Tachypnea (rapid breathing) such as in transient tachypnea of the newborn, surfactant deficiency, respiratory distress syndrome or other infant medical conditions...
of machine perfusion aimed at sustaining the active aerobic cellular metabolism of donor lungs outside the donor's body prior to lung transplantation...
; Zhao, Xiubo; Cooper, Alan; Kennedy, Malcolm W. (2009). "Latherin: A Surfactant Protein of Horse Sweat and Saliva". PLoS One. 4 (5): e5726. doi:10.1371/journal...
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