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Thorax 68:460-467 doi:10.1136/thoraxjnl-2012-202729
  • Paediatric lung disease
  • Original article

Increased prevalence of low oligomeric state surfactant protein D with restricted lectin activity in bronchoalveolar lavage fluid from preterm infants

  1. Eamon P McGreal1
  1. 1Department of Child Health, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
  2. 2Royal Hospital for Sick Children, Yorkhill, Glasgow, UK (current address)
  3. 3Department of Child Health, NIHR Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
  1. Correspondence to Dr Eamon P McGreal, Department of Child Health, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK; mcgrealep{at}cf.ac.uk
  • Received 13 September 2012
  • Revised 14 December 2012
  • Accepted 11 January 2013
  • Published Online First 6 February 2013

Abstract

Background Surfactant protein D (SP-D) is a soluble oligomeric C-type lectin known to protect against lipopolysaccharide and ventilator-induced lung injury in preterm lambs. Here we assess the expression and functional status of SP-D in bronchoalveolar lavage fluid (BALF) from preterm infants at risk of chronic lung disease (CLD) of prematurity and term controls. This is the first systematic evaluation of SP-D function in any clinical cohort.

Methods SP-D was quantified in BALF from 28 ventilated preterm infants and five ventilated term infants. SP-D lectin activity was tested in a zymosan binding assay followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blot in BALF from the same infants. SP-D lectin activity was also tested towards maltose-agarose and mannan for selected BALF samples.

Results SP-D expression was lower on day 1 in those preterm infants who subsequently developed CLD but increased over the first 5 days of life in term and preterm neonates. The percentage of neonatal SP-D capable of binding zymosan rarely exceeded 50% in any BALF sample and was 3.5 times lower in preterm infants than term infants on day 1 of life. Similar binding defects were observed towards maltose-agarose and mannan. SDS-PAGE analysis revealed that zymosan-bound SP-D was more highly oligomerised (≥12-mers) than unbound SP-D, which was composed primarily of trimers and lower oligomeric forms.

Conclusions Substantial and functionally relevant variation in the expression and oligomeric distribution of SP-D exists between preterm and term neonatal lung secretions. This has implications for proposed SP-D replacement therapy in this population.