The vitamin D axis in the lung: a key role for vitamin D-binding protein
Thorax 2010;65:456-462 doi:10.1136/thx.2009.128793
1. L Chishimba1,
2. D R Thickett2,
3. R A Stockley3,
4. A M Wood2
1.Burton Hospital NHS Trust, Burton-on-Trent, UK
2College of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
3Lung Investigation Unit, University Hospitals Birmingham, Birmingham, UK
1. Correspondence to Dr A M Wood, Lung Investigation Unit, University Hospitals Birmingham, Birmingham B15 2TH, UK; a.m.wood at bham.ac.uk
* Received 12 October 2009, * Accepted 23 December 2009
There has been much recent interest in the role of the vitamin D axis in lung disease, which includes vitamin D, vitamin D receptor (VDR) and vitamin D-binding protein (VDBP; also known as Gc-globulin). VDBP is a serum protein which has immunomodulatory functions relevant in the lung, predominantly relating to macrophage activation and neutrophil chemotaxis. Variations within its gene are also associated with airways disease, implying a role for the protein product in pathogenesis. Thus far the majority of evidence relates to chronic obstructive pulmonary disease (COPD), but is scant in other airways diseases, such as asthma and bronchiectasis. VDBP also acts as a scavenger protein to clear extracellular G-actin released from necrotic cells, which may be of relevance in severe lung infections and acute lung injury. Vitamin D protects against the development of cancer and tuberculosis, although optimal levels are unknown. The majority of circulating vitamin D is bound to VDBP, and its uptake into cells occurs in both bound and unbound forms, which suggests the role of VDBP warrants further study in these conditions as well. This article reviews the evidence of the role VDBP and its gene (GC) in a range of lung diseases, including asthma, COPD and tuberculosis.