title: Pulmonary collectins play distinct roles in host defense against Mycobacterium avium.
abstract: Pulmonary collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), play important roles in the innate immunity of the lung. Mycobacterium avium is one of the well-known opportunistic pathogens that can replicate within macrophages. We examined the effects of pulmonary collectins in host defense against M. avium infection achieved via direct interaction between bacteria and collectins. Although both pulmonary collectins bound to M. avium in a Ca(2+)-dependent manner, these collectins revealed distinct ligand-binding specificity and biological activities. SP-A and SP-D bound to a methoxy group containing lipid and lipoarabinomannan, respectively. Binding of SP-D but not SP-A resulted in agglutination of M. avium. A chimeric protein with the carbohydrate recognition domain of SP-D, which chimera revealed a bouquet-like arrangement similar to SP-A, also agglutinated M. avium. The ligand specificity of the carbohydrate recognition domain of SP-D seems to be necessary for agglutination activity. The binding of SP-A strongly inhibited the growth of M. avium in culture media. Although pulmonary collectins did not increase membrane permeability of M. avium, they attenuated the metabolic rate of the bacteria. Observations under a scanning electron microscope revealed that SP-A almost completely covers bacterial surfaces, whereas SP-D binds to certain areas like scattered dots. These observations suggest that a distinct binding pattern of collectins correlates with the difference of their biological activities. Furthermore, the number of bacteria phagocytosed by macrophages was significantly increased in the presence of SP-D. These data indicate that pulmonary collectins play critical roles in host defense against M. avium.
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. sarikscb@sapmed.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ariki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Shinsei
authors.initials: S
authors.lastname: Gasa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kurimura
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
mesh_terms: D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D009162:Mycobacterium avium / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011485:Protein Binding; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology* / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000276:immunology* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020349:Surface Plasmon Resonance; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D