Shah Chandrabala, Hari-Dass Ranjeeta, Raynes John G
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St, London WCIE 7HT, United Kingdom.
Blood. 2006 Sep 1;108(5):1751-7. doi: 10.1182/blood-2005-11-011932. Epub 2006 May 30.
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.
血清淀粉样蛋白A（SAA）是人类和大多数哺乳动物中的主要急性期蛋白。最近我们证明，SAA通过外膜蛋白A（OmpA）家族成员与许多革兰氏阴性菌结合，包括大肠杆菌和铜绿假单胞菌。因此，我们研究了SAA是否改变了天然吞噬细胞对细菌的反应。SAA调理作用使含有大肠杆菌的中性粒细胞百分比和每个中性粒细胞内的细菌数量都大大增加，相当于血清调理作用所观察到的增加。相比之下，肺炎链球菌（一种不与SAA结合的细菌）则没有变化。SAA调理作用还增加了细菌刺激下中性粒细胞活性氧中间产物的产生。SAA调理作用也增加了外周血单核细胞来源的巨噬细胞对大肠杆菌的吞噬作用。这些巨噬细胞对SAA调理的大肠杆菌和铜绿假单胞菌表现出TNF-α和IL-10产生的强烈增强。在存在SAA不结合的细菌时，SAA不会增强反应。SAA的这些作用在与SAA结合特性及其在天然识别中的作用一致的正常浓度下发生。因此，SAA代表了一种针对革兰氏阴性菌的新型天然识别蛋白。
