The collectins are a family of homo trimeric protein that dimerize to form hexameric complexes, each subunit of which contains a collagen-like tail connected by a neck region to a calcium-dependent (C-type) lectin head. Three members of this family serve as soluble effector molecules in the innate immune system; these are MBL and pulmonary surfactant proteins SP-A and SP-D.
• MBL, which is a soluble pattern recognition receptor that binds carbohydrates with terminal mannose and fucose, was discussed earlier in relation to the lectin pathway of complement activation (Fig. 1). MBL also functions as an opsonin by binding to and enhancing phagocytosis of microbes. Recall that opsonins simultaneously bind microbes and a surface receptor on phagocyte membranes, and in the case of MBL, the surface receptor is called the C1q receptor because it also binds C1q. This receptor mediates the internalization of microbes that are opsonized by MBL. The gene encoding MBL is polymorphic, and certain alleles are associated with impaired hexamer formation and reduced blood levels. Low MBL levels result in increased susceptibility to a variety of infections, especially in individuals who have other immune defects.
• Surfactant protein A (SP-A) and D (SP-D) are collectins with lipophilic properties shared by other surfactants. They are found in the alveoli of the lungs, and their major functions are to maintain the ability of alveoli to expand upon inhalation by reducing the surface tension of alveolar fluid, and as mediators of innate immune responses in the lung. They bind to various microorganisms and act as opsonins, facilitating ingestion of the microbes by alveolar macrophages. SP-A and SP-D can also directly inhibit bacterial growth and they may activate macrophages. SP-A– and SP-D–deficient mice have impaired abilities to resist a variety of pulmonary infections.
Fig1. C1, mannose-binding lectin, and ficolin. These three homologous hexameric proteins can all initiate complement activation on binding to their ligands on cell surfaces. C-type lectin–like globular heads (H) at the end of collagenous-like stalks in the C1q and mannose-binding lectin proteins bind the Fc regions of immunoglobulin M (IgM) or mannose on the surface of microbes, respectively. Fibrinogen-like globular heads on ficolin bind N-acetylglucosamine on the surface of microbes. Binding results in conformational changes that activate the serine protease activity of C1r and C1s, associated with C1q, or mannose-associated serine protease 1 (MASP1) and MASP2, associated with mannose-binding lectin and ficolin.
Ficolins are plasma proteins that are structurally similar to collectins. They possess a collagen-like domain, but instead of a C-type lectin domain, they have a fibrinogen-type carbohydrate recognition domain (see Fig. 1). Ficolins have been shown to bind several species of bacteria, opsonizing them and activating complement in a manner similar to that of MBL. The ligands of the ficolins include N-acetylglucosamine and the lipoteichoic acid component of the cell walls of gram-positive bacteria.
