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.
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan. kuroki@sapmed.ac.jp
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Kuroki
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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