A direct role for vitamin D-binding protein in the pathogenesis of COPD?
- MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, London, UK
- Correspondence to Catherine Hawrylowicz, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King's College London, London SE1 9RT, UK;
Epidemiological studies support the importance of adequate vitamin D status for the maintenance of pulmonary health and function; low levels of serum 25-hydroxyvitamin D3 are associated with an increased incidence or poor control of asthma, respiratory infection and chronic obstructive pulmonary disease (COPD).1–4 Vitamin D is proposed to support respiratory health through promoting antimicrobial functions necessary for efficient clearance of pathogens, and dampening inflammation with the potential to damage lung structure and impair gaseous exchange.4 However, the role of its major carrier protein, vitamin D-binding protein (VDBP), is less well understood. A paper by Wood et al in Thorax5 together with independent studies, highlight the potential of VDBP to influence respiratory function both by determining vitamin D bioavailability and via direct effects on innate cell function.
VDBP is a glycosylated α-globulin protein synthesised by many tissues including the liver, kidneys, gonads and fat, and also by neutrophils. It binds circulating 25(OH)-vitamin D and 1,25(OH)2-vitamin D with high affinity. The levels of this protein far exceed circulating levels of these vitamin D metabolites, although VDBP has a rapid turnover rate. VDBP has three distinct domains which confer additional functions beyond carriage of vitamin D (reviewed by Chishimba et al6). These functions include augmentation of the monocyte and neutrophil chemotactic response to the complement anaphylotoxin C5a,7 8 scavenging of actin molecules released from necrotic cells9 and, of interest to the current article, formation of a dimeric molecule with macrophage activating factor (DBP-MAF) which drives macrophages towards a more phagocytic phenotype with increased superoxide generation.10 These activities of VDBP may be of particular …