Serum amyloid A is an innate immune opsonin for Gram-negative bacteria.
Serum amyloid A (SAA) is the major acute-phase protein in man and most mammals. Recently we demonstrated that SAA binds to many Gram-negative bacteria including Escherichia coli and Pseudomonas aeruginosa through outer membrane protein A (OmpA) family members. Therefore we investigated whether SAA altered the response of innate phagocytic cells to bacteria. Both the percentage of neutrophils containing E coli and the number of bacteria per neutrophil were greatly increased by SAA opsonization, equivalent to the increase seen for serum opsonization. In contrast, no change was seen for Streptococcus pneumoniae, a bacteria that did not bind SAA. Neutrophil reactive oxygen intermediate production in response to bacteria was also increased by opsonization with SAA. SAA opsonization also increased phagocytosis of E coli by peripheral blood mononuclear cell-derived macrophages. These macrophages showed strong enhancement of TNF-alpha and IL-10 production in response to SAA-opsonized E coli and P aeruginosa. SAA did not enhance responses in the presence of bacteria to which it did not bind. These effects of SAA occur at normal concentrations consistent with SAA binding properties and a role in innate recognition. SAA therefore represents a novel innate recognition protein for Gram-negative bacteria.
Shah
Chandrabala
C
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WCIE 7HT, United Kingdom.
Hari-Dass
Ranjeeta
R
Raynes
John G
JG
D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018613:Microscopy, Confocal; D009504:Neutrophils / Q000502:physiology*; D009895:Opsonin Proteins / Q000494:pharmacology*; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000276:immunology; D012016:Reference Values; D016897:Respiratory Burst; D000685:Serum Amyloid A Protein / Q000276:immunology* / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology
D009895:Opsonin Proteins; D000685:Serum Amyloid A Protein