Surfactant protein a regulates complement activation

Complement proteins aid in the recognition and clearance of pathogens from the body. C1, the first protein of the classical pathway of complement acti vation, is a calcium-dependent complex of one molecule of C1q and two molec ules each of Or and C1s, the serine proteases that cleave complement protei ns. Upon binding of C1q to Ag-bound IgG or IgM, C1r and C1s are sequentiall y activated and initiate the classical pathway of complement. Because of st ructural and functional similarities between C1q and members of the collect in family of proteins, including pulmonary surfactant protein A (SP-A), we hypothesized that SP-A may interact with and regulate proteins of the compl ement system. Previously, SP-A was shown to bind to C1q, but the functional significance of this interaction has not been investigated. Binding studie s confirmed that SP-A binds directly to C1q, but only weakly to intact C1. Further investigation revealed that the binding of SP-A to C1q prevents the association of C1q with C1r and Cls, and therefore the formation of the ac tive C1 complex required for classical pathway activation. This finding sug gests that SP-A may share a common binding site for C1r and C1s or C1q. SP- A also prevented C1q and C1 from binding to immune complexes. Furthermore, SP-A blocked the ability of Clq to restore classical pathway activity to C1 q-depleted serum. SP-A may down-regulate complement activity through its as sociation with C1q. We hypothesize that SP-A may serve a protective role in the lung by preventing C1q-mediated complement activation and inflammation along the delicate alveolar epithelium.