Serum amyloid P component bound to gram-negative bacteria prevents lipopolysaccharide-mediated classical pathway complement activation
Serum amyloid P component bound to gram-negative bacteria prevents lipopolysaccharide-mediated classical pathway complement activation
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DOI：
10.1128/iai.68.4.1753-1759.2000
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发表时间：
2000-04-01
影响因子：
3.1
通讯作者：
van Strijp, JAG
中科院分区：
文献类型：
--
作者：
de Haas, CJC;van Leeuwen, EMM;van Strijp, JAG
虽然已知血清淀粉样蛋白P组分（SAP）结合多种配体，但其生物学功能尚不清楚。最近，研究表明SAP与脂多糖（LPS）结合。在本研究中，SAP显示与表达短型LPS或脂寡糖（LOS）的革兰氏阴性细菌（如沙门氏菌（Salmonella enterica serovar Copenhagen Re）和大肠杆菌J5）结合，并且还与流感嗜血杆菌（Haemophilus influenzae）的临床分离株结合。假设SAP通过LPS或LOS的脂质A部分与细菌结合，因为不可分型的H.表达非乙酰化脂质A的流感病毒株NTHi 2019-B29-3不结合SAP。这与亲本菌株NTHi 2019相反，SAP的结合导致补体组分C3在细菌上的沉积的明显抑制。SAP仅抑制经典补体途径的激活;替代途径不受影响。在经典途径中，SAP可能通过干扰Clq与LPS的结合来阻止第一补体组分Clq的沉积。由于抗体介导的Clq活化不受SAP抑制，因此SAP似乎仅抑制LPS诱导的经典补体途径活化。SAP诱导的C3沉积抑制强烈减弱了补体介导的溶解以及细菌的吞噬作用。因此，SAP与革兰氏阴性菌的结合可能会影响此类细菌感染的病理生理学。
Although serum amyloid P component (SAP) is known to bind many ligands, its biological function is not yet clear. Recently, it was demonstrated that SAP binds to lipopolysaccharide (LPS), In the present study, SAP was shown to bind to gram-negative bacteria expressing short types of LPS or lipo-oligosaccharide (LOS), such as Salmonella enterica serovar Copenhagen Re and Escherichia coli J5, and also to clinical isolates of Haemophilus influenzae. It was hypothesized that SAP binds to the bacteria via the lipid A part of LPS or LOS, since the htrB mutant of the nontypeable H. influenzae strain NTHi 2019-B29-3, which expresses a nonacetylated lipid A, did not bind SAP. This was in contrast to the parental strain NTHi 2019, The binding of SAP resulted in a clear inhibition of the deposition of complement component C3 on the bacteria. SAP inhibited only the activation of the classical complement pathway; the alternative route remained unaffected. In the classical route, SAP prevented the deposition of the first complement component, Clq, probably by interfering with the binding of Clq to LPS. Since antibody-mediated Clq activation was not inhibited by SAP, SAP seems to inhibit only the LPS-induced classical complement pathway activation. The SAP-induced inhibition of C3 deposition strongly diminished the complement-mediated lysis as well as the phagocytosis of the bacteria. The binding of SAP to gram-negative bacteria, therefore, might influence the pathophysiology of an infection with such bacteria.