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.
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 degrees C but not at 4 degrees 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.
Kuronuma
Koji
K
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
Sano
Hitomi
H
Kato
Kazunori
K
Kudo
Kazumi
K
Hyakushima
Naoki
N
Yokota
Shin-ichi
S
Takahashi
Hiroki
H
Fujii
Nobuhiro
N
Suzuki
Hiroshi
H
Kodama
Tatsuhiko
T
Abe
Shosaku
S
Kuroki
Yoshio
Y
D000107:Acetylation; D019943:Amino Acid Substitution; D000818:Animals; D047390:Casein Kinase II; D002462:Cell Membrane / Q000502:physiology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000382:microbiology* / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000378:metabolism; D051117:Scavenger Receptors, Class A; D013296:Streptococcus pneumoniae / Q000502:physiology*
D008077:Lipoproteins, LDL; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; D051117:Scavenger Receptors, Class A; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases