Pulmonary Surfactant Protein A Augments the Phagocytosis of Streptococcus pneumoniae by Alveolar Macrophages through a Casein Kinase 2-dependent Increase of Cell Surface Localization of Scavenger Receptor A

• Published in: The Journal of biological chemistry 2004-05, Vol.279 (20), p.21421-21430
• Main Authors: Kuronuma, Koji, Sano, Hitomi, Kato, Kazunori, Kudo, Kazumi, Hyakushima, Naoki, Yokota, Shin-ichi, Takahashi, Hiroki, Fujii, Nobuhiro, Suzuki, Hiroshi, Kodama, Tatsuhiko, Abe, Shosaku, Kuroki, Yoshio
• Format: Article
• Language: English
• Subjects: Acetylation; Amino Acid Substitution; Animals; Casein Kinase II; Cell Membrane - physiology; Kinetics; Lipoproteins, LDL - metabolism; Macrophages, Alveolar - microbiology; Macrophages, Alveolar - physiology; Phagocytosis - physiology; Protein-Serine-Threonine Kinases - metabolism; Pulmonary Surfactant-Associated Protein A - genetics; Pulmonary Surfactant-Associated Protein A - metabolism; Pulmonary Surfactant-Associated Protein D - genetics; Pulmonary Surfactant-Associated Protein D - metabolism; Rats; Receptors, Immunologic - metabolism; Receptors, Scavenger; Recombinant Proteins - metabolism; Scavenger Receptors, Class A; Streptococcus pneumoniae; Streptococcus pneumoniae - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M312490200

Pulmonary surfactant proteins A (SP-A) and D (SP-D), members of the collectin family, play important roles in the innate immune system of the lung. Here, we show that SP-A but not SP-D augmented phagocytosis of Streptococcus pneumoniae by alveolar macrophages, independent of its binding to the bacteria. Analysis of the SP-A/SP-D chimeras, in which progressively longer carboxyl-terminal regions of SP-A were replaced with the corresponding SP-D regions, has revealed that the SP-D region Gly 346 -Phe 355 can be substituted for the SP-A region Leu 219 -Phe 228 without altering the SP-A activity of enhancing the phagocytosis and that the SP-A region Cys 204 -Cys 218 is required for the SP-A-mediated phagocytosis. Acetylated low density lipoprotein significantly reduced the SP-A-stimulated uptake of the bacteria. SP-A failed to enhance the phagocytosis of S. pneumoniae by alveolar macrophages derived from scavenger receptor A (SR-A)-deficient mice, demonstrating that SP-A augments SRA-mediated phagocytosis. Preincubation of macrophages with SP-A at 37 °C but not at 4 °C stimulated the phagocytosis. The SP-A-mediated enhanced phagocytosis was not inhibited by the presence of cycloheximide. SP-A increased cell surface localization of SR-A that was inhibitable by apigenin, a casein kinase 2 (CK2) inhibitor. SP-A-treated macrophages exhibited significantly greater binding of acetylated low density lipoprotein than nontreated cells. The SP-A-stimulated phagocytosis was also abolished by apigenin. In addition, SP-A stimulated CK2 activity. These results demonstrate that SP-A enhances the phagocytosis of S. pneumoniae by alveolar macrophages through a CK2-dependent increase of cell surface SR-A localization. This study reveals a novel mechanism of bacterial clearance by alveolar macrophages.