Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism
- K J Fidler1,
- T N Hilliard2,3,
- A Bush2,3,
- M Johnson4,
- D M Geddes5,
- M W Turner4,
- E W F W Alton2,
- N J Klein1,
- J C Davies2,3
- 1Infectious Diseases and Microbiology Unit, Institute of Child Health, London, UK
- 2Department of Gene Therapy, Imperial College, London, UK
- 3Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK
- 4Immunobiology Unit, Institute of Child Health, London, UK
- 5Thoracic Medicine, Royal Brompton Hospital, London, UK
- Dr J C Davies, Department of Gene Therapy, Imperial College, London SW3 6LR, UK;
- Received 4 April 2008
- Accepted 23 September 2008
- Published Online First 6 November 2008
Background: Mannose-binding lectin (MBL) deficiency has been associated with infections of the respiratory tract and with increased disease severity in cystic fibrosis (CF). The mechanism is uncertain, and could relate either to systemic or local effects. The aim of this study was to determine, in a large cohort of children, whether MBL is present on the airway surface in health or disease.
Methods: Bronchoalveolar lavage (BAL) fluid from children with and without respiratory infection (some with underlying disease) was analysed for MBL and neutrophil elastase (NE). Levels were compared between groups, and correlations were examined with local and systemic inflammatory markers, infective organisms and load.
Results: 85 children were recruited to the study. MBL was absent in the lavage of all 7 children without lung infection but present in 62% (8/13) of those with acute pneumonia/pneumonitis, 23% (5/22) with recurrent respiratory tract infections, 17% (1/6) with primary ciliary dyskinesia and 8% (3/37) with CF (p<0.01). Children with acute pneumonia/pneumonitis had significantly higher levels than those in the other groups. There was no relationship with organisms cultured or systemic markers of inflammation, although in the group with detectable MBL in the BAL fluid, the levels correlated positively with levels of NE.
Conclusions: MBL is undetectable in the non-infected airway but is present in a significant number of samples from children with lung infection. The levels found in the BAL fluid could be physiologically active and the protein may therefore be playing a role in host defence.
Funding: This work was supported by the following foundations: The Wellcome Trust- Training Fellowship (KJF) and Senior Research Fellowship (EWFWA); Cystic Fibrosis Trust (JCD). Work in the Institute of Child Health is also supported by The Wellcome Trust, EU Grant Contract No. QLRT-CT-2001-01039 and by Action Research. Research at the Institute of Child Health and Great Ormond Street Hospital for Children National Health Service (NHS) Trust benefits from research and development funding received from the UK NHS Executive.
Competing interests: MWT and NJK act as scientific consultants for NatImmune, a Danish company exploring the therapeutic potential of mannose-binding lectin.
Ethics approval: Local research ethics committee approval was obtained from Great Ormond Street Hospital and The Royal Brompton, Harefield and NHLI Trust. All parents or carers gave informed consent and assent was obtained from children where appropriate.