Immunomodulatory roles of surfactant proteins A and D: implications in lung disease

Abstract

Surfactant, a lipoprotein complex, was originally described for its essential role in reducing surface tension at the air-liquid interface of the lung; however, it is now recognized as being a critical component in lung immune host defense. Surfactant proteins (SP)-A and -D are pattern recognition molecules of the collectin family of C-type lectins. SP-A and SP-D are part of the innate immune system and regulate the functions of other innate immune cells, such as macrophages. They also modulate the adaptive immune response by interacting with antigen-presenting cells and T cells, thereby linking innate and adaptive immunity. Emerging studies suggest that SP-A and SP-D function to modulate the immunologic environment of the lung so as to protect the host and, at the same time, modulate an overzealous inflammatory response that could potentially damage the lung and impair gas exchange. Numerous polymorphisms of SPs have been identified that may potentially possess differential functional abilities and may act via different receptors to ultimately alter the susceptibility to or severity of lung diseases.

Figure 1.

Collectin structure. (a) Surfactant protein (SP)–A and SP-D are members of the collectin family that function as pattern recognition molecules. Collectins are composed of an N-terminal noncollagenous domain and of a C-type (calcium-dependent) carbohydrate recognition domain (CRD; lectin domain). (b) Structurally, collectins are trimeric polypeptide chains that are assembled into oligomers; SP-A and mannose-binding lectin (MBL) are octodecamers, consisting of six trimeric subunits, and SP-D is a dodecomer, consisting of four trimeric subunits. Models are not drawn to scale. Reprinted by permission from Reference 2.

Figure 2.

Functions of SP-A and SP-D as collectins. SP-A and SP-D bind to and opsonize viruses, bacteria, allergens, and apoptotic cells. SP-A and SP-D enhance microbial phagocytosis by aggregating bacteria and viruses. SP-A and SP-D also possess direct bactericidal effects and potentially bind to a variety of receptors to modulate immune cell cytokine and inflammatory mediator expression. Reprinted by permission from Reference 2.

Figure 3.

SP-A and SP-D link innate and adaptive immunity to regulate host defense. Although both SP-A and SP-D can bind to T cells and directly inhibit proliferation, SP-A can also indirectly inhibit T-cell proliferation via suppression of dendritic cell (DC) maturation. SP-D has been shown to enhance antigen uptake and presentation. Taken together, these in vitro results suggest that the combined role of SP-A and SP-D is to modulate the immunologic environment of the lung so as to protect the host, yet thwart an overzealous inflammatory response that could potentially damage the lung and impair gas exchange. Reprinted by permission from Reference 2.