title: Surfactant protein A regulates complement activation.
abstract: Complement proteins aid in the recognition and clearance of pathogens from the body. C1, the first protein of the classical pathway of complement activation, is a calcium-dependent complex of one molecule of C1q and two molecules each of C1r and C1s, the serine proteases that cleave complement proteins. Upon binding of C1q to Ag-bound IgG or IgM, C1r and C1s are sequentially activated and initiate the classical pathway of complement. Because of structural and functional similarities between C1q and members of the collectin family of proteins, including pulmonary surfactant protein A (SP-A), we hypothesized that SP-A may interact with and regulate proteins of the complement system. Previously, SP-A was shown to bind to C1q, but the functional significance of this interaction has not been investigated. Binding studies 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 C1s, and therefore the formation of the active C1 complex required for classical pathway activation. This finding suggests that SP-A may share a common binding site for C1r and C1s or Clq. SP-A also prevented C1q and C1 from binding to immune complexes. Furthermore, SP-A blocked the ability of C1q to restore classical pathway activity to C1q-depleted serum. SP-A may down-regulate complement activity through its association 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.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Watford
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
authors.forename: C G
authors.initials: CG
authors.lastname: Hester
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: M M
authors.initials: MM
authors.lastname: Frank
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology*; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D003172:Complement C1 / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism / Q000502:physiology; D015922:Complement C1q / Q000037:antagonists & inhibitors / Q000378:metabolism; D015923:Complement C1r / Q000037:antagonists & inhibitors / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D011485:Protein Binding / Q000276:immunology; D011510:Proteolipids / Q000378:metabolism / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D015922:Complement C1q; D015923:Complement C1r; D003173:Complement C1s