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

Kotecha, Sailesh, Davies, Philip Lloyd, Clark, Howard W. and McGreal, Eamon Patrick 2013. Increased prevalence of low oligomeric state surfactant protein D with restricted lectin activity in bronchoalveolar lavage fluid from preterm infants. Thorax 68 (5) , pp. 460-467. 10.1136/thoraxjnl-2012-202729

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Publisher: BMJ Publishing Group
ISSN: 0040-6376
Last Modified: 04 Jun 2017 05:18
URI: http://orca-mwe.cf.ac.uk/id/eprint/50494

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