Functional roles and structural analysis of lung collectins SP-A and SP-D.
Pulmonary surfactant proteins A and D (SP-A and SP-D) belong to the collectin subgroup of the C-type lectin superfamily along with mannose-binding protein (MBP) and conglutinin. Phospholipids are also ligands for collectins, in addition to carbohydrates and glycosphingolipids. SP-A binds dipalmitoylphosphatidylcholine, and SP-D and MBP bind phosphatidylinositol. SP-A also interacts with alveolar type II cells, implicating SP-A in surfactant phospholipid homeostasis. We analyzed an epitope for anti-SP-A monoclonal antibodies that block SP-A-specific functions using a phage display peptide library and SP-A/MBP chimeric proteins. We also investigated the regions of SP-A and SP-D that are required for ligand interactions using SP-A/SP-D chimeras. Lung collectins play key roles in the innate immune system of the lung which is critical for immediate antibody-independent host defense. We have found that SP-A exhibits different interactions with distinct serotypes of lipopolysaccharides and affects differently their elicited cellular responses by a direct interaction with the lipopolysaccharide receptor CD14. In addition to the basic aspects, lung collectins as clinical markers will be discussed.
Kuroki
Y
Y
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan. kuroki@sapmed.ac.jp
Sano
H
H
D001665:Binding Sites; D015415:Biomarkers; D006023:Glycoproteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D018410:Pneumonia, Bacterial / Q000517:prevention & control; D011510:Proteolipids / Q000737:chemistry* / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000502:physiology*
D015415:Biomarkers; D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants