Complement system in lung disease

Abstract

In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions.

Keywords: fibrosis; immune complexes; immunology; transplantation.

Figure 1.

Complement pathways. Three pathways are known to activate the complement cascade. The classical pathway is initiated through binding of C1q protein to Fc receptor on the antibody–antigen complex. Activation of the lectin pathway is mediated through mannose-binding lectin that binds mannose (carbohydrates) on pathogens’ surface. Alternative pathway act as an amplification loop by spontaneously hydrolyzing C3 to initiate complement activation. All three pathways converge to form C3 convertase, which downstream leads to assembly of C5 converatase, thus forming membrane attack complex (MAC), which results in cell death. The complement pathways can be regulated at the level of C3 and C5 convertases or at MAC.

Figure 2.

Model of immune complex–mediated lung injury. (A) Normal airways. (B) Injury to the lung can be mediated by immune complex–mediated injury in the lung epithelium. Antigen inhaled or present in the lung is bound by its antibody. C1q binds to the Fc portion of the antibody and activates complement cascade. (C) Lung injury can also initiate inflammation by complement activation through local synthesis of complement proteins from alveolar macrophages or airway epithelium. (D) Lung inflammation is exacerbated by complement proteins that act as chemoattractants for neutrophils.