Congenital pulmonary alveolar proteinosis: Failure of treatment with extracorporeal life support

Moulton, Steven L.; Krous, Henry F.; Merritt, T. Allen; Odell, Richard M.; Gangitano, Ernesto; Cornish, J. Devn

doi:10.1016/s0022-3476(05)80448-2

Cited by 48 publications

(26 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this pattern is consistent neither with the morphology nor location of the infiltrates observed in ␤cR KO mice before or after BMT. 3,4,14 Taken together, these observations suggest that the cellular infiltrate observed in KO mice after WT BMT is part of a fixed, recipient-derived process which is thought to be directly related to the ␤cR mutation rather than secondary to the proteinosis. 1 Although the residual cellular histopathology is mild, it is likely responsible for the incomplete improvement in C dyn and lack of improvement in G L that was seen despite the complete resolution of alveolar proteinosis in the WT → KO group.…”

Section: Recipients Despite the Resolution Of Alveolar Proteinosis Afmentioning

confidence: 99%

“…Abnormalities include lymphocytic infiltration around airways and vessels and the progressive accumulation of surfactant proteins, Mice deficient for the IL-3/GM-CSF/IL-5 ␤c receptor (␤cR KO) develop lung disease similar to that seen in phospholipids and macrophages within the alveolar space. [1][2][3][4][5] Previous work has defined a significant part of this disease human pulmonary alveolar proteinosis (PAP) which includes lymphocytic infiltration around airways and to be hematopoietic in origin because transplantation of wild-type (WT) bone marrow into ␤cR KO mice led to vessels and the progressive accumulation of surfactant and macrophages within the alveolar space. We investicomplete resolution of alveolar proteinosis and restoration of normal macrophage morphology.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 β c receptor-deficient mice despite correction of alveolar proteinosis after BMT

Cooke

Nishinakamura²,

Martin

et al. 1997

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:pulmonary alveolar proteinosis (PAP). Abnormalities include lymphocytic infiltration around airways and vessels and the progressive accumulation of surfactant proteins, Mice deficient for the IL-3/GM-CSF/IL-5 ␤c receptor (␤cR KO) develop lung disease similar to that seen in phospholipids and macrophages within the alveolar space. [1][2][3][4][5] Previous work has defined a significant part of this disease human pulmonary alveolar proteinosis (PAP) which includes lymphocytic infiltration around airways and to be hematopoietic in origin because transplantation of wild-type (WT) bone marrow into ␤cR KO mice led to vessels and the progressive accumulation of surfactant and macrophages within the alveolar space. We investicomplete resolution of alveolar proteinosis and restoration of normal macrophage morphology. When the lungs of ␤cR gated bone marrow transplantation (BMT) as a curative treatment of PAP in ␤cR KO mice by semiquantitative KO mice were evaluated at 8 and 12 weeks after WT BMT however, it was apparent that residual lung injury was histologic analysis and evaluation of pulmonary function. BMT from wild-type (WT) donors into lethally present despite the dramatic improvement in the disease state. 6 In order to determine the precise effects of BMT in irradiated ␤cR KO recipients (WT → KO) led to the complete resolution of alveolar protein accumulation the reversal of the mutant phenotype, we examined more closely the extent of residual disease in these animals postand to normalization of BAL fluid cellularity and macrophage morphology. However, detailed microtransplant by using a semiquantitative index for histopathology, and correlated these findings to pulmonary function. scopic analysis of lung tissue revealed the persistence of significant cellular infiltrates in WT → KO recipients Our findings demonstrate that abnormal respiratory physiology and significant mononuclear cell infiltrates remain in which were equivalent to those seen in KO → KO animals. Evaluation of pulmonary function demonstrated ␤cR KO mice despite the marked improvement in alveolar protein accumulation after WT BMT. that only dynamic compliance (C dyn ) and not airway conductance (G L ) was significantly improved in the WT → KO group compared to KO → KO animals and that both of these measurements remained significantly Materials and methods abnormal when compared to WT → WT controls. We conclude, that although BMT for PAP reverses alveolar Mice and bone marrow transplantation macrophage and protein accumulation, it does not decrease the interstitial inflammatory component of this Generation of mice deficient for the ␤c receptor (␤cR KO) and methods for BMT have been described previously. 1,6 disease. The importance of this residual pathology is demonstrated by the incomplete correction of alveolar Briefly, all experimental animals were raised and housed in microisolator cages at the DNAX animal facility and have function (C dyn ) and lack of improvement in increased airway resistance (G L ). These findings may have routinely ...

show abstract

Section: Recipients Despite the Resolution Of Alveolar Proteinosis Afmentioning

confidence: 99%

mentioning

confidence: 99%

Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 β c receptor-deficient mice despite correction of alveolar proteinosis after BMT

Cooke

Nishinakamura²,

Martin

et al. 1997

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…SP-B deficiency is a genetic disorder which occurs in (mature) newborns with severe respiratory distress at birth. Despite extracorporeal membrane oxygenation [137], glucocorticoids and exogenous surfactant substitution [138,139], this condition leads to death within the first year of life. BAL reveals a lack of SP-B and abundant aberrant pro-SP-C. Immunohistological studies of lung tissue show quantitative and qualitative abnormalities of SP-A and SP-C [140].…”

Section: Congenital Diaphragmatic Herniamentioning

confidence: 99%

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

Dai¹,

Guzman²,

Costabel³

1999

Eur Respir J

View full text Add to dashboard Cite

The Fas receptor (FasR) and the tumour necrosis factor (TNF) receptor 55/60 kDa (TNFR1) are recognized as apoptosis signalling receptors. They are known to be expressed by lymphocytes in association with immune regulation and immunological disorders. This study aimed to investigate the expression of FasR and TNFR1 by alveolar macrophages (AM) in patients with sarcoidosis. Bronchoalveolar lavage (BAL) was performed in 12 patients with active sarcoidosis and 11 control subjects. BAL cells were characterized by monoclonal antibodies using a peroxidase-antiperoxidase method. Both FasR and TNFR1 were expressed on a higher percentage of AM in sarcoidosis with respect to control subjects (mean +/-sem 40.8+/-3.1% versus 14.9+/-1.7%, p<0.001 and 61.9+/-3.3% versus 23.1+/-4.1%, p<0.001, respectively). There was a close relationship between the expression of FasR and TNFR1 on AM (r = 0.86, p<0.001). The percentages of FasR+ AM and TNFR1+ AM were in direct proportion to the percentage of BAL lymphocytes (r = 0.75 and 0.84), the CD4/CD8 ratio (r = 0.78 and 0.78), and the percentage of the CD14+ AM subset (r = 0.77 and 0.87), p<0.001 for all correlations. This study indicates that alveolar macrophages expressing apoptotic receptors are increased in patients with active sarcoidosis. Further studies are required to determine whether these alveolar macrophages from patients with sarcoidosis undergo apoptosis more readily than those from control subjects.

show abstract

“…A deficiency of surfactant protein B (SP-B), ' an 8,000-D lungspecific protein, was recently demonstrated in three full-term siblings who died from respiratory failure associated with histopathologic changes of alveolar proteinosis (2). SP-B has an important role in the surface tension-lowering properties of pulmonary surfactant, and congenital alveolar proteinosis (CAP) is a recognized familial cause offatal respiratory disease in full-term infants (3)(4)(5)(6). These observations suggest that an inherited deficiency of SP-B may cause this disorder and that abnormalities of surfactant proteins due to genetic mechanisms could cause respiratory disease.…”

Section: Introductionmentioning

confidence: 99%

A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds.

Nogee¹,

Garnier²,

Dietz³

et al. 1994

J. Clin. Invest.

525

327

View full text Add to dashboard Cite

To determine the molecular defect accounting for the deficiency of pulmonary surfactant protein B (SP-B) in full-term neonates who died from respiratory failure associated with alveolar proteinosis, the sequence of the SP-B transcript in affected infants was ascertained. A frameshift mutation consisting of a substitution of GAA for C in codon 121 of the SP-B cDNA was identified. The three affected infants in the index family were homozygous for this mutation, which segregated in a fashion consistent with autosomal recessive inheritance of disease. The same mutation was found in two other unrelated infants who died from alveolar proteinosis, one of whom was also homozygous, and in the parents of an additional unrelated, affected infant, but was not observed in 50 control subjects. We conclude that this mutation is responsible for SP-B deficiency and neonatal alveolar proteinosis in multiple families and speculate that the disorder is more common than was recognized previously. (J.

show abstract

Congenital pulmonary alveolar proteinosis: Failure of treatment with extracorporeal life support

Cited by 48 publications

References 11 publications

Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 β c receptor-deficient mice despite correction of alveolar proteinosis after BMT

Persistence of pulmonary pathology and abnormal lung function in IL-3/GM-CSF/IL-5 β c receptor-deficient mice despite correction of alveolar proteinosis after BMT

Increased expression of apoptosis signalling receptors by alveolar macrophages in sarcoidosis

A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds.

Contact Info

Product

Resources

About