Regulation of protein phosphorylation and pathogen phagocytosis by surfactant protein A.
Surfactant protein A (SP-A), a pulmonary member of the collectin family of proteins, facilitates the rapid clearance of pathogens by upregulating immune cell functions in the lungs. SP-A binds to bacteria and targets them for rapid phagocytosis by alveolar macrophages, but the mechanism by which this stimulation occurs is not clear. To characterize the intracellular events that may be involved, we examined the roles of protein phosphorylation and cytoskeletal polymerization in SP-A-stimulated phagocytosis. In rat alveolar macrophages, SP-A stimulated rapid tyrosine phosphorylation of specific proteins in a dose- and time-dependent manner. The pattern of proteins that were phosphorylated in response to SP-A, as resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was similar to that observed for immunoglobulin G (IgG)-stimulated macrophages. Both SP-A and IgG stimulated increases in phagocytosis of Streptococcus pneumoniae above levels in the absence of added protein by 394% +/- 81% and 200% +/- 25%, respectively. Phagocytosis in both cases was dependent on tyrosine kinases, protein kinase C, and actin polymerization but not on microtubule activity. These studies show that SP-A utilizes pathways similar to those used by IgG to increase macrophage phagocytosis of bacteria.
Schagat
T L
TL
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Tino
M J
MJ
Wright
J R
JR
D000818:Animals; D003599:Cytoskeleton; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D015739:Nocodazole / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism* / Q000494:pharmacology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013296:Streptococcus pneumoniae / Q000276:immunology*
D007074:Immunoglobulin G; D011506:Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D019833:Genistein; D015739:Nocodazole; D004121:Dimethyl Sulfoxide