Abstract
BackgroundSurfactant proteins SP-A and SP-D are useful biomarkers in diagnosis, monitoring, and prognosis of idiopathic pulmonary fibrosis (IPF). Despite their high structural homology, their serum concentrations often vary in IPF patients. This retrospective study aimed to investigate distinct compartmentalization of SP-A and SP-D in the vasculature and lungs by bronchoalveolar lavage fluid (BALF)/serum analysis, hydrophilicity and immunohistochemistry.MethodsWe included 36 IPF patients, 18 sarcoidosis (SAR) patients and 20 healthy subjects. Low-speed centrifugal supernatants of BALF (Sup-1) were obtained from each subject. Sera were also collected from each patient. Furthermore, we separated Sup-1 of IPF patients into hydrophilic supernatant (Sup-2) and hydrophobic precipitate (Ppt) by high-speed centrifugation. We measured SP-A and SP-D levels of each sample with the sandwich ELISA technique. We analyzed the change of the BALF/serum level ratios of the two proteins in IPF patients and their hydrophilicity in BALF. The distribution in the IPF lungs was also examined by immunohistochemical staining.ResultsIn BALF, SP-A levels were comparable between the groups; however, SP-D levels were significantly lower in IPF patients than in others. Although IPF reduced the BALF/serum level ratios of the two proteins, the change in concentration of SP-D was more evident than SP-A. This suggests a higher disease impact for SP-D. Regarding hydrophilicity, although more than half of the SP-D remained in hydrophilic fractions (Sup-2), almost all of the SP-A sedimented in the Ppt with phospholipids. Hydrophilicity suggests that SP-D migrates into the blood more easily than SP-A in IPF lungs. Immunohistochemistry revealed that SP-A was confined to thick mucus-filling alveolar space, whereas SP-D was often intravascular. This data also suggests that SP-D easily leaks into the bloodstream, whereas SP-A remains bound to surfactant lipids in the alveolar space.ConclusionsThe current study investigated distinct compartmentalization of SP-A and SP-D in the vasculature and lungs. Our results suggest that serum levels of SP-D could reflect pathological changes of the IPF lungs more incisively than those of SP-A.
Highlights
Surfactant proteins surfactant protein (SP)-A and SP-D are useful biomarkers in diagnosis, monitoring, and prognosis of idiopathic pulmonary fibrosis (IPF)
It has been reported that serum SP-D were median 19.1 (SP-A) and SP-D concentrations are elevated in IPF and other interstitial lung diseases, and that they can predict the progression of respiratory failure and prognosis in IPF [5,6]
As an example for this variability, we presented the difference of serum concentration of these proteins between IPF patients with ground glass opacities (GGO) and patients with consolidationdominant opacities by computed tomography [5]
Summary
Surfactant proteins SP-A and SP-D are useful biomarkers in diagnosis, monitoring, and prognosis of idiopathic pulmonary fibrosis (IPF) Despite their high structural homology, their serum concentrations often vary in IPF patients. The pulmonary surfactant consists of phospholipids, mainly dipalmitoyl phosphatidylcholine (DPPC), surfactant protein (SP)-A, SP-B, SP-C, and SP-D. Both SP-A and SP-D are produced by type II alveolar epithelial cells and Clara cells, and are secreted into the alveolar space [1,2]. Unlike SP-B and SP-C, they are hydrophilic proteins belonging to the C-type lectin superfamily Both SP-A and SP-D play crucial roles in lung innate immunity [3,4]. Whereas SP-A binds to DPPC and galactosylceramide, SP-D binds to phosphatidylinositol and glucosylceramide [9,10,11,12]
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