The roles of surfactant proteins A and D in innate immunity.
Research over the last decade on the surfactant proteins SP-A and SP-D suggests roles beyond surfactant lipid homeostasis, involving their participation in innate immune defence. SP-A and SP-D bind and agglutinate an impressive array of non-self structures, ranging from bacteria and fungi to allergens and environmental inorganic substrates. Complementing binding. SP-A and SP-D initiate and enhance immune cell ingestion and killing of targets. Recently, some exciting developments have extended and clarified their contributions to innate immunity. Knockout mice for SP-A and SP-D have been developed. The SP-A knockout confirms that SP-A plays a key role in defence against lung pathogens and reveals the underlying defense mechanisms that require SP-A. These surfactant proteins have also been shown to have important roles in modulating the immune response, instructing, yet quenching, the immune reactions in the lung. The crystal structure of SP-D plus functional studies with recombinantly altered forms of SP-A and SP-D has begun to characterise the structural motifs responsible for mediating their immune functions. Linkage and polymorphism analysis is explaining the role these genes may play in lung diseases and infection.
Lawson
P R
PR
Department of Biochemistry, Oxford University, England.
Reid
K B
KB
D001665:Binding Sites; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000235:genetics; D008168:Lung / Q000276:immunology*; D008958:Models, Molecular; D011485:Protein Binding; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D037102:Lectins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants