Human surfactant protein B: structure, function, regulation, and genetic disease

Whitsett, JA; Nogee, Lawrence M.; Weaver, Timothy E.; Horowitz, Ann D.

doi:10.1152/physrev.1995.75.4.749

Cited by 180 publications

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“…In mice it has been demonstrated that only the animals homozygous for this allele were affected [40]. Interestingly, to date, six different mutations in this gene were identified [345]. The SP-B deficiency is associated with SP-A and SP-C abnormalities.…”

Section: Disorders Of Surfactantmentioning

confidence: 99%

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The Pulmonary Surfactant System: Biochemical and Clinical Aspects

Creuwels

Golde

Haagsman

1997

Lung

283

188

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Abstract. This article starts with a brief account of the history of research on pulmonary surfactant. We will then discuss the morphological aspects and composition of the pulmonary surfactant system. We describe the hydrophilic surfactant proteins A and D and the hydrophobic surfactant proteins B and C, with focus on the crucial roles of these proteins in the dynamics, metabolism, and functions of pulmonary surfactant. Next we discuss the major disorders of the surfactant system. The final part of the review will be focused on the potentials and complications of surfactant therapy in the treatment of some of these disorders. It is our belief that increased knowledge of the surfactant system and its functions will lead to a more optimal composition of the exogenous surfactants and, perhaps, widen their applicability to treatment of surfactant disorders other than neonatal respiratory distress syndrome.Key words: Surfactant protein-Pulmonary surfactant-Respiratory distress syndrome. HistoryResearch on surfactant goes back to 1929 when von Neergaard published the first paper about the difference in pressure needed to inflate lungs with air or with liquid [333]. He found that the pressure necessary for filling the lungs with air was higher than when the lungs were filled with liquid. To explain this result he stated that the alveoli were stabilized by lowering the naturally high surface tension of the air/water interface. In 1946 Thannhauser and co-workers reported that lung tissue has a remarkably high content of the lipid dipalmityl lecithin (current name, dipalmitoylphosphatidylcholine)Offprint requests to: Henk P. Haagsman.

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Section: Disorders Of Surfactantmentioning

confidence: 99%

“…The results of the treatment of infants suffering from this disease are still very poor. Up to now, total cardiopulmonary support, involving extracorporeal membrane oxygenation, repeated surfactant instillations, and corticosteroid therapy has not led to successful treatment [114,345].…”

Section: Disorders Of Surfactantmentioning

confidence: 99%

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

Creuwels

Golde

Haagsman

1997

Lung

283

188

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“…4). Homozygous mutations leading to the complete absence of SP-B in newborn human infants result in the rapid onset of respiratory distress syndrome which is refractory to mechanical ventilation and surfactant replacement (5,6).…”

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confidence: 99%

Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein

Akinbi

Breslin

Ikegami

et al. 1997

Journal of Biological Chemistry

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Pulmonary surfactant is a complex mixture of lipids and proteins that is synthesized exclusively by the alveolar type II epithelial cell. Surfactant is stored in large inclusions (lamellar bodies) that are secreted into the alveolar airspace by exocytosis. Newly secreted lamellar bodies unravel into a tubular network (tubular myelin) that subsequently adsorbs and spreads as a phospholipid-rich film that reduces surface tension at the air-liquid interface. Rapid adsorption and spreading of the phospholipid film are critical and require the presence of specific proteins, in particular surfactant proteins B and C (1-3).Surfactant protein B (SP-B) 1 is a hydrophobic peptide of 79 amino acids that avidly associates with surfactant phospholipids in the alveolar airspace (reviewed in Ref. 4). Homozygous mutations leading to the complete absence of SP-B in newborn human infants result in the rapid onset of respiratory distress syndrome which is refractory to mechanical ventilation and surfactant replacement (5, 6). The latter observation suggests that simple addition of mature peptide to the SP-B-deficient airway is not sufficient to restore lung function. Therefore, despite an obvious requirement for SP-B in normal lung function, the precise role(s) of SP-B in the structure, function, and metabolism of surfactant remains unclear.Human SP-B is synthesized by the type II epithelial cell as a preproprotein of 381 amino acids. The mature peptide is generated by sequential cleavage of the signal peptide (23 amino acids), the N-terminal propeptide (177 residues), and the Cterminal propeptide (102 residues) (7, 8). Propeptide cleavage occurs within the late endosome/multivesicular body which subsequently directs newly synthesized SP-B to the lamellar body (9); mature SP-B is also recycled from the alveolar airspace, via the endocytic pathway to the multivesicular body (10). Previous in vitro evidence supports the concept that trafficking of the mature peptide through the biosynthetic pathway requires the N-terminal but not the C-terminal domain of the propeptide (11,12). In the absence of both propeptide domains the mature peptide is degraded within the endoplasmic reticulum (11); however, an SP-B construct encoding both the Nterminal propeptide and the mature peptide (hSP-B ⌬c ) produces a truncated proprotein that is sorted to the multivesicular body where the propeptide is appropriately cleaved to liberate mature SP-B (12). These results clearly demonstrate that the N-terminal propeptide is required for the intracellular trafficking of SP-B; the function of the C-terminal propeptide, however, remains unknown.Lung morphogenesis and surfactant phospholipid synthesis in SP-B(Ϫ/Ϫ) mice proceed normally prior to birth (13). However, lamellar body formation is disrupted, resulting in abnormal inclusions consisting of multivesicular bodies and disorganized lamellae. Neither mature lamellar bodies nor tubular myelin were detected in the SP-B(Ϫ/Ϫ) mice. In addition to effects on lamellar body biogenesis, SP-B deficiency resulted in

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“…SP-C is the smallest (4.2-8 kDa) and the most hydrophobic surfactant protein (with 70 % of hydrophobic amino acids), and is only found in the lungs (Glasser et al, 2001). SP-B is an 8.7-kDa-protein component of tubular myelin, and enhances adsorption and re-spreading (Whitsett et al, 1995;Oviedo et al, 2001). SP-B is required for normal lung function (Melton et al, 2003;Nesslein et al, 2005).…”

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confidence: 99%

Hypobaric hypoxia-related impairment of pulmonary surfactant proteins A and D did not favourPneumocystis cariniiFrenkel 1999 growth in non-immunocompromised rats

Vives

Caspar-Bauguil²,

Aliouat

et al. 2008

Parasite

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Summary :It has been suggested that patients with pulmonary surfactant impairment are more susceptible to Pneumocystis infection than healthy controls. Owing the fact that most patients with pulmonary surfactant impairment also suffer from hypoxia, we explored the effect of intermittent hypobaric hypoxia conditions on the ability of non-immunocompromised rats infected by endotracheal route with P. carinii to clear the infection from their lungs. Control rats, inoculated or not with P. carinii, were maintained in normobaric normoxic conditions, and were submitted or not to dexamethasone administration. It was found that even if hypobaric hypoxia weakened host immune mechanisms and impaired significantly the surfactant composition, mainly of surfactant proteins A and D, these changes were not enough to favour the Pneumocystis growth or to inhibit the clearing of Pneumocystis organisms from the lungs of non-immunocompromised rats. The potential influence of surfactant protein changes on Pneumocystis infection is discussed. Résumé : DES ALTÉRATIONS DES

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Human surfactant protein B: structure, function, regulation, and genetic disease

Cited by 180 publications

References 0 publications

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein

Hypobaric hypoxia-related impairment of pulmonary surfactant proteins A and D did not favourPneumocystis cariniiFrenkel 1999 growth in non-immunocompromised rats

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