Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis

Abstract

Alveolar proteinosis (AP) is an idiopathic condition characterized by excess alveolar surfactant. Although the surfactant proteins (SP) are known to be aberrant, little is known of their variation between patients or their abundance relative to the lipids. We have examined surfactant composition in lavage fluid from 16 normal subjects and 13 patients with AP, one of whom was lavaged on 11 occasions over approximately 13 mo. In this patient we have examined composition on each occasion and in each sequential lavage aliquot. Composition was constant between right and left lung, but it differed markedly between patients. The cholesterol/disaturated phospholipid ratios (CHOL/DSP) were invariably elevated, on average by approximately 7-fold, whereas the SP-A/DSP and SP-B/DSP ratios were generally elevated, in some cases by as much as approximately 40- and approximately 100-fold, respectively. Although AP lavage generally contained more non-thiol-dependent SP-A aggregates and low Mr isoforms, the two-dimensional immunochemical staining patterns varied between patients and right and left lung. In the patient lavaged on multiple occasions, the SP-A/DSP and SP-B/DSP ratios progressively decreased as the patient's condition resolved. Because the SP-B/SP-A ratio was normal in all cases, we suggest that structural changes to the proteins occurred secondarily and that caution must be used in comparing functional data derived using SP-A obtained from patients with AP.

Surfactant protein A and other bronchoalveolar lavage fluid proteins are altered in cystic fibrosis

“…The molecular weight and pI of the main chain of SP-A isomers are not altered in CF and are also in accordance with reports in the literature [22,23]. BAKER et al [24] and DOYLE et al [25] previously described the qualitative impairment of SP-A in BALF of patients with acute respiratory distress syndrome [25] and of patients with pulmonary alveolar proteinosis [25] compared to controls. Both found alterations in the distribution between polymeric and isomeric forms of SP-A, but no LMW products of SP-A (MW <24 kD).…”

“…These forms of SP-A were likely to represent dimers and oligomers [25], but it is not known how they are generated and what their exact functional role is. A quantitative reduction of SP-A in BALF from CF patients with severe lung disease has been reported previously [13,14], whereas in asymptomatic CF infants no alterations and with infection an upregulation of SP-A has been noted [27].…”

Targeted PPARγ deficiency in alveolar macrophages disrupts surfactant catabolism

“…Consistent with the fi ndings in PAP patients and GM-CSF KO mice (37)(38)(39)(40)(41), the MacPPAR ␥ KO mice exhibit e levated levels of the major lipid components of surfactant, including cholesterol and phospholipid, in the BAL fl uid and alveolar macrophages. The alveolar macrophages from the MacPPAR ␥ KO mice had signifi cant accumulation of free (unesterifi ed) cholesterol.…”

Serum cholestenoic acid as a potential marker of pulmonary cholesterol homeostasis

“…In accordance with earlier findings (10,22), total cholesterol levels were found to be significantly increased ( P ϭ 0.011) in BAL fluid from PAP patients (6.9 Ϯ 1.14 mg/ml; n ϭ 14) compared with healthy controls (3.3 Ϯ 0.64 mg/ml; n ϭ 13) ( Fig. 2 ).…”