Removal of a dimeric form of surfactant protein C from mouse lungs: its acceleration by reduction

Li, Zhongyuan; Suzuki, Yuzuru; Kurozumi, Mafumi; Shen, Hui-Qing; Duan, Chen-Xia

doi:10.1152/jappl.1998.84.2.471

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…However, dimeric SP-C may be causally related to the intraalveolar accumulation of surfactant proteins, since it is cleared from lungs with an increased half-life, it is not removed from alveolar macrophages, and it hinders clearance of SP-B and monomeric SP-C by alveolar macrophages. Furthermore, dimeric SP-C is toxic to alveolar macrophages through an increased formation of reactive oxygen species [45,46]. Importantly, the pathology observed here cannot be attributed to a lack of mature SP-C, but rather resulted from a deleterious gain of function induced by expression products of the mutant allele.…”

Section: Discussionmentioning

confidence: 72%

“…Dimeric SP-C forms of y7-9 kDa consisting of non-or monopalmitoylated SP-C have been found in adult patients suffering from PAP [44][45][46]. Palmitoylation of proSP-C does not appear to be related to proprotein targeting, as substitution of the cystein residues normally undergoing palmitoylation did not influence the sorting of the protein [39].…”

Section: Discussionmentioning

confidence: 97%

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Interstitial lung disease in a baby with ade novomutation in the SFTPC gene

Brasch

Griese²,

Tredano³

et al. 2004

Eur Respir J

144

132

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Mutations in the surfactant protein C gene (SFTPC) were recently reported in patients with interstitial lung disease.In a 13‐month-old infant with severe respiratory insufficiency, a lung biopsy elicited combined histological patterns of nonspecific interstitial pneumonia and pulmonary alveolar proteinosis. Immunohistochemical and biochemical analyses showed an intra-alveolar accumulation of surfactant protein (SP)‐A, precursors of SP‐B, mature SP‐B, aberrantly processed proSP‐C, as well as mono- and dimeric SP‐C.Sequencing of genomic DNA detected ade novoheterozygous missense mutation of the SFTPC gene (g.1286T>C) resulting in a substitution of threonine for isoleucine (I73T) in the C‐terminal propeptide. At the ultrastructural level, abnormal transport vesicles were detected in type‐II pneumocytes. Fusion proteins, consisting of enhanced green fluorescent protein and wild-type or mutant proSP‐C, were used to evaluate protein traffickingin vitro. In contrast to wild-type proSP‐C, mutant proSP‐C was routed to early endosomes when transfected into A549 epithelial cells.In contrast to previously reported mutations, the I73T represents a new class of surfactant protein C gene mutations, which is marked by a distinct trafficking, processing, palmitoylation, and secretion of the mutant and wild-type surfactant protein C. This report heralds the emerging diversity of phenotypes associated with the expression of mutant surfactant C proteins.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 97%

Interstitial lung disease in a baby with ade novomutation in the SFTPC gene

Brasch

Griese²,

Tredano³

et al. 2004

Eur Respir J

144

132

View full text Add to dashboard Cite

show abstract

“…However, dimeric SP-C might be causally related to the intra-alveolar accumulation of surfactant proteins; since it is cleared from lungs with an increased half-life, it is not removed from alveolar macrophages and it hinders clearance of SP-B and monomeric SP-C by alveolar macrophages. Furthermore, dimeric SP-C is toxic to alveolar macrophages via an increased formation of reactive oxygen species [39,40].…”

Section: Discussionmentioning

confidence: 99%

Surfactant proteins in pulmonary alveolar proteinosis in adults

Brasch

Birzele²,

Ochs³

et al. 2004

Eur Respir J

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Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised histologically by an intra-alveolar accumulation of fine granular eosinophilic and periodic acid-Schiff positive material.In a retrospective study, the composition of the intra-alveolarly accumulated material of adult patients with PAP was analysed by means of immunohistochemistry and Western blotting.In patients with PAP, the current authors found an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, SP-B, variable amounts of mono-, di-, and oligomeric SP-C forms, as well as SP-D. Only in one patient was a precursor of SP-C detected. By means of immuno-electron microscopy, the current authors identified not only transport vesicles labelled for precursors of SP-B and SP-C, but also transport vesicles containing either precursors of SP-B or SP-C in type-II pneumocytes in normal human lungs.It is concluded that pulmonary alveolar proteinosis in adults is characterised by an intra-alveolar accumulation of surfactant protein A, precursors of surfactant protein B, and surfactant proteins B, C and D. The current data provide evidence that not only an impairment of surfactant clearance by alveolar macrophages, but also an abnormal secretion of transport vesicles containing precursors of surfactant protein B (but not surfactant protein C) and an insufficient palmitoylation of surfactant protein C, which may lead to the formation of di-and oligomeric surfactant protein C forms, play a role in the pathogenesis of pulmonary alveolar proteinosis. Eur Respir J 2004; 24: 426-435.

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“…In GM‐CSF knockout mice, as well as in SP‐D knockout mice, the alveolar macrophages have been reported to be loaded with lipoproteinaceous material [13,24,25]. The clearance of alveolar SP‐C fibrils is expected to be significantly impaired compared to that of native SP‐C, since already dimeric/depalmitoylated SP‐C is cleared from mouse lungs with a half‐life which is more than twice that for monomeric/native SP‐C [26]. Clearance of surfactant phospholipids and SP‐A is, however, also impaired in PAP [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…4). Previous studies have revealed elevated levels of depalmitoylated forms of SP‐C in PAP compared to healthy controls [26,35]. Protein palmitoylation often occurs in integral membrane proteins close to their transmembrane helices [36], but the biological function of this modification is not known.…”

Section: Discussionmentioning

confidence: 99%

Amyloid fibril formation by pulmonary surfactant protein C

et al. 1999

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Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric K K-helix into L L-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.z 1999 Federation of European Biochemical Societies.

show abstract

Removal of a dimeric form of surfactant protein C from mouse lungs: its acceleration by reduction

Cited by 6 publications

References 29 publications

Interstitial lung disease in a baby with ade novomutation in the SFTPC gene

Interstitial lung disease in a baby with ade novomutation in the SFTPC gene

Surfactant proteins in pulmonary alveolar proteinosis in adults

Amyloid fibril formation by pulmonary surfactant protein C

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