Abstract
BackgroundThe state of oligomerization of surfactant associated protein-A (SP-A) monomers differs between individuals. This likely affects SP-A’s functional properties and could thereby influence clinical status in patients with lung diseases. In this study we focus on SP-A structure in cystic fibrosis (CF) compared to both healthy subjects and disease controls.MethodsSP-A composition and function were assessed in both bronchoalveolar lavage (BAL) fluid and serum of 46 CF patients with mild disease, 25 patients with chronic bronchitis and 22 healthy subjects by gel chromatography and a functional agglutination assay. Relation of SP-A agglutination ability to disease severity of the subjects was explored.ResultsSP-A was present in seven major oligomeric forms with the majority of SP-A being structurally organized as complex oligomeric forms. More complex oligomeric forms were associated with better SP-A function with regard to its agglutination ability. These forms were more frequently observed in BAL than in serum, but there were no differences between disease groups. In CF patients, more complex forms of SP-A were associated with better lung function.ConclusionsOrganizational structure of SP-A affects its functional activity and is linked to disease severity in CF.
Highlights
Surfactant associated protein-A (SP-A) is the most abundant pulmonary surfactant protein and belongs to the family of innate host defense proteins termed collectins
Cystic fibrosis (CF) is a life limiting disease associated with chronic pulmonary infections [8]
Bronchoalveolar lavage (BAL) levels of surfactant associated protein-A (SP-A) have been shown to be increased early in the course of the disease [9], but decrease as disease progresses and lower levels are correlated with more inflammation and diminished lung function [10,11,12,13,14,15]
Summary
Ethics Statement The study was approved by the institutional review board, the Ethics committee of the Medical Faculty of the LMU Munich (EK 026-06) and all participants gave their written informed consent. Gel Chromatography To determine the structural organization of SP-A in BAL and serum gel chromatography on a superpose 6 column was used as described in previous studies [6,7]. This method separates SP-A molecules with regard to their oligomerization form. SP-A present in each of the fractions from gel chromatography was determined by slot blot (see below) and the amounts of the different structures were calculated from the area under the curve of the corresponding peak as a percentage of total amounts of SPA present (Fig. 1). The agglutinates were photographed at 10 fold magnification, the pictures viewed with Adobe Photoshop software and the size of all the agglutinates (typically more than 100) was assessed and the largest measured in pixels by drawing squares around them and averaged by a blinded examiner with regard to the diagnosis [19]
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