Complement-mediated host defense in the lung

Complement is a system of plasma proteins that aids in the elimination of pathogens from the body. We hypothesized that there is a functional complement system present in the lung that aids in the removal of pathogens. Western blot analysis revealed complement proteins of the alternative and classical pathways of complement in bronchoalveolar lavage fluids (BALF) from healthy volunteers. Functional classical pathway activity was detected in human BALF, but there was no significant alternative pathway activity in lavage fluid, a finding that correlates with the low level of the alternative pathway protein, factor B, in these samples. Although the classical pathway of complement was functional in lavage fluid, the level of the classical pathway activator C1q was very low. We tested the ability of the lung- specific surfactant proteins, surfactant protein A (SP-A) and surfactant protein D (SP-D), to substitute for C1q in classical pathway activation, since they have structural homology to C1q. However, neither SP-A nor SP-D restored classical pathway activity to C1q-depleted serum. These data suggest that the classical pathway of complement is functionally active in the lung where it may play a role in the recognition and clearance of bacteria.