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

• Published in: Thorax Vol. 68; no. 5; pp. 460 - 467
• Main Authors: Kotecha, Sailesh, Davies, Philip L, Clark, Howard W, McGreal, Eamon P
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Thoracic Society 01.05.2013; BMJ Publishing Group LTD
• Subjects: Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Infant, Premature; Inflammation; Innate Immunity; Lavage; Lectins; Lung - metabolism; Lung diseases; Male; Newborn babies; Paediatric Lung Disaese; Premature babies; Premature birth; Proteins; Pulmonary Surfactant-Associated Protein D - biosynthesis; Respiration, Artificial; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - metabolism; Respiratory Distress Syndrome, Newborn - therapy; Statistical analysis; Surfactant protein; Surfactants; Ventilators; United Kingdom > UK
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2012-202729

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.