Background Progranulin (PGRN) is an anti-inflammatory protein, which is converted into pro-inflammatory granulin peptides (GRNs) by neutrophil elastase (NE) and proteinase-3 (PR3) (1). Neutrophilic inflammation is implicated in the pathophysiology of COPD, therefore the influence of PGRN on mechanisms of neutrophilic inflammation may be of great relevance to understanding and treating inflammation in the disease.
Methods Sputum and serum samples were obtained from COPD patients with chronic bronchitis at exacerbation and in the subsequent clinically stable state. Sputum samples were graded by purulence and cultured for quantitative microbiology. PGRN was measured in sputum sol phase together with leukotriene B4 (LTB4), interleukin 8 (IL-8), myeloperoxidase (MPO), tumour necrosis factor α (TNFα), NE and PR3. PGRN and C-reactive protein (CRP) were measured in the serum.
Results PGRN was lower in purulent sputum (median=38.91 ng/ml (IQR=1.55–89.71 ng/ml)) than mucoid (median=79.78 ng/ml (IQR=51.57–111.24 ng/ml)) (p=0.024, n=69). In purulent sputum PGRN correlated negatively with bacterial load and markers of inflammation (Table 1). Serum PGRN did not correlate with CRP, but was higher in stable COPD patients (median=65.71 ng/ml (IQR=0–86.46 ng/ml)) than healthy controls (median=38.55 ng/ml (IQR=36.11–44.82 ng/ml)) (p=<0.001, n=20), and increased further during purulent exacerbations (median=75.43 ng/ml (IQR=64.83–85.28 ng/ml)) (p=0.010, n=25).
Conclusion The concentration of PGRN in the lung is associated with the increased inflammation seen with bacterial infection and exacerbation as assessed by markers of inflammation. The conversion of PGRN to GRNs may provide a mechanism by which neutrophil proteases regulate inflammation in COPD. Elevated circulating PGRN may reflect systemic inflammation associated with COPD.
Kessenbrock K, et al. J Clin Invest. 2008 Jul; 118(7):2438–47.