Fig. 5

A model of the effects of cigarette smoke on the small airway protein profile. A Cigarette smoke consists of gaseous and particulate matter (tar) phase and the ROS in cigarette smoke induce oxidative stress. B Particulate matter causes an increase in ferritin levels in RTLF and affects fibrinogen and plasma kallikrein levels. Plasma kallikrein plays a role in the contact activation, coagulation and the alternative complement pathway. C Oxidative stress causes cell damage or apoptosis. Levels of TCTP, which protects cells from the apoptotic cell death, were increased in current smokers. Protein S, which is involved in the inhibition of coagulation and clearance of apoptotic cells was decreased in current smokers. In a complex with C4BP, protein S also prevents excessive complement activation and inflammation on the surface of apoptotic cells. sRAGE inhibits the induction of pro-inflammatory responses caused by the activation of RAGE signalling and decreased levels of sRAGE may contribute to inflammation. Upregulation of pro-inflammatory proteins and cytokines occurs due to oxidative stress and FSTL3 acts by neutralizing the activity of these proteins and induces the production of anti-inflammatory cytokines. Additionally, ROS cause damage to proteins, lipids and DNA and impair protein folding. Increased expression of heat shock proteins in the lungs exposed to cigarette smoke promotes the repair of misfolded proteins. Decreased levels of SPOCK2, which provides protection against influenza virus infection, may contribute to inflammation by making the epithelial cells more susceptible to viral infections. D Changes in the forementioned proteins all contribute to promoting inflammation and our findings suggest an important role of the complement system in this process. A decrease in CD55 and factors H and I, important inhibitors of complement activation, was observed in female current smokers, which could lead to excessive complement activation resulting in the depletion of C3 and C5, and this could be an important initiating step in the pathogenesis of small airway inflammation