Pulmonary Collectins Protect Macrophages against Pore-forming Activity of Legionella pneumophila and Suppress Its Intracellular Growth
| Autor: | Yoshio Kuroki, Shin-ichi Yokota, Nobuhiro Fujii, Norimasa Sawada, Motoko Takahashi, Hiroaki Mitsuzawa, Chiaki Nishitani, Atsushi Saito, Shigeru Ariki, Masami Yamazoe, Takashi Kojima, Takeyuki Shimizu, Hiroki Takahashi, Kaku Sawada |
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| Rok vydání: | 2010 |
| Předmět: |
Lipopolysaccharides
Phagocytosis Immunology Carbohydrates Collectin Biochemistry Legionella pneumophila Monocytes Cell Line Microbiology Macrophages Alveolar Humans Macrophage Pulmonary Surfactant-Associated Protein D Molecular Biology Phagosome Pulmonary Surfactant-Associated Protein A Innate immune system biology Cell Membrane Cell Biology bacterial infections and mycoses biology.organism_classification respiratory tract diseases bacteria Calcium Legionnaires' Disease Lysosomes |
| Zdroj: | Journal of Biological Chemistry. 285:8434-8443 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.074765 |
| Popis: | Pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), play important roles in innate immunity of the lung. Legionella pneumophila is a bacterial respiratory pathogen that can replicate within macrophages and causes opportunistic infections. L. pneumophila possesses cytolytic activity, resulting from insertion of pores in the macrophage membrane upon contact. We examined whether pulmonary collectins play protective roles against L. pneumophila infection. SP-A and SP-D bound to L. pneumophila and its lipopolysaccharide (LPS) and inhibited the bacterial growth in a Ca(2+)-dependent manner. The addition of LPS in the culture blocked the inhibitory effects on L. pneumophila growth by the collectins, indicating the importance of LPS-collectin interaction. When differentiated THP-1 cells were infected with L. pneumophila in the presence of SP-A and SP-D, the number of permeable cells was significantly decreased, indicating that pulmonary collectins inhibit pore-forming activity of L. pneumophila. The number of live bacteria within the macrophages on days 1-4 after infection was significantly decreased when infection was performed in the presence of pulmonary collectins. The phagocytosis experiments with the pH-sensitive dye-labeled bacteria revealed that pulmonary collectins promoted bacterial localization to an acidic compartment. In addition, SP-A and SP-D significantly increased the number of L. pneumophila co-localized with LAMP-1. These results indicate that pulmonary collectins protect macrophages against contact-dependent cytolytic activity of L. pneumophila and suppress intracellular growth of the phagocytosed bacteria. The promotion of lysosomal fusion with Legionella-containing phagosomes constitutes a likely mechanism of L. pneumophila growth suppression by the collectins. |
| Databáze: | OpenAIRE |
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