Complement Factor C5a in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abstract

The complement component C5a is a potent inflammatory peptide, which may be involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We analysed the induced sputum and plasma of 28 patients with stable COPD, 12 healthy smokers and 7 non‐smokers. In 13 of the patients with COPD, we also observed paired samples during acute exacerbation. The concentrations of C5a/C5a desArg and C3a/C3a desArg were measured using cytometric bead array. Both C5a and C3a concentrations in induced sputum of stable patients with COPD were significantly increased compared to the control groups of healthy smokers and non‐smokers. In addition, there was a significant elevation in C5a values in exacerbation of COPD that was independent from the airway C3a levels. Airway C5a levels were negatively correlated with forced expiratory volume in first second (FEV1)% predicted and diffusing capacity of the lung (TLCO). Plasma C5a concentrations in patients with COPD were significantly higher than in healthy smokers, but no further significant systemic C5a elevation was detected with acute exacerbation of COPD. There was no important difference in local or systemic C5a concentrations between healthy smokers and non‐smokers. These in vivo results clearly show that local and systemic C5a concentrations in COPD are elevated, and that the local, in contrast to systemic, C5a concentrations additionally increase in the acute exacerbation of COPD. It seems that the cigarette smoke is not related to C5a increase. The elevated local and systemic C5a levels, and additional individual local C5a increase during the exacerbation support the importance of C5a in COPD.

The role of complement activation in COPD exacerbation recovery

“…Significant increases in both sputum C3a and C5a were found during COPD exacerbations compared with baseline; this was consistent with previous studies, two of which found sputum C5a elevated [1, 5] and another demonstrated C3a elevation at exacerbation [10]. The opposite was seen for serum C3a and C5a, in which we found significantly lower levels during exacerbations.…”

“…Complement anaphylatoxins (C3a, C5a) are potent inflammatory mediators, implicated in the exaggerated inflammatory response seen in chronic obstructive pulmonary disease (COPD) [1]. COPD patients have decreased levels of serum C3 and C4 [2, 3], and higher levels of sputum C3a and C5a, than healthy volunteers [4].…”

“…COPD patients have decreased levels of serum C3 and C4 [2, 3], and higher levels of sputum C3a and C5a, than healthy volunteers [4]. Both sputum and serum C5a levels climb during acute exacerbations [1, 5]. Serum C5a during COPD exacerbations has been positively correlated with C-reactive protein (CRP) and negatively correlated with percentage predicted forced expiratory volume in 1 s (FEV 1 % pred) [5].…”

Oxidative Stress–induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease

“…Moreover, they found a correlation between the degree of the reduction of these serum proteins and the presence of symptoms of chronic bronchitis (41). In contrast, Marc and colleagues demonstrated that sputum levels of both C3a and C5a were significantly increased in patients with moderate to severe stable COPD compared with control healthy smokers and nonsmokers (42). Together this would suggest that as complement is sequestered toward the lung where it is activated and consumed, serum levels would decline.…”

Blood Specimen Biomarkers of Inflammation, Matrix Degradation, Angiogenesis, and Cardiac Involvement: a Future Useful Tool in Assessing Clinical Outcomes of COPD Patients in Clinical Practice?

“…In this study in patients with stable COPD we found elevated in vivo levels of C5a in induced sputum compared to healthy non-smoking subjects. In our later work (Marc et al 2010), we studied the airway and systemic levels of C5a and C3a in patients with COPD during the stable phase and during acute exacerbation of the disease. For this purpose we analyzed induced sputum and plasma samples of 28 patients with COPD.…”