Microparticle-associated tissue factor activity is reduced by inhibition of the complement protein 5 in Neisseria meningitidis-exposed whole blood

被引:22
作者
Ovstebo, Reidun [1 ]
Hellum, Marit [1 ,4 ]
Aass, Hans Christian D. [1 ]
Troseid, Anne M. [1 ]
Brandtzaeg, Petter [2 ,4 ]
Mollnes, Tom E. [3 ,4 ]
Henriksson, Carola E. [1 ]
机构
[1] Oslo Univ Hosp, Dept Med Biochem, Blood Cell Res Grp, N-0407 Oslo, Norway
[2] Oslo Univ Hosp, Dept Pediat, N-0407 Oslo, Norway
[3] Oslo Univ Hosp, Dept Immunol, N-0407 Oslo, Norway
[4] Univ Oslo, Inst Clin Med, N-0316 Oslo, Norway
关键词
Neisseria meningitidis; TF activity; monocytes; microparticles; complement cascade; coagulation cascade; THROMBIN GENERATION; FACTOR EXPRESSION; MODEL; C5A; COAGULATION; ACTIVATION; INFLAMMATION; DECREASES; PLASMA; PCR;
D O I
10.1177/1753425913502099
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neisseria meningitidis causes fulminant meningococcal sepsis with a massive activation of the coagulation and complement cascades. Bacterial cell envelope molecules from N. meningitidis, particularly lipopolysaccharide (LPS), induce tissue factor (TF) expression. In meningococcal sepsis, TF can be detected on circulating monocytes and microparticles (MPs) within the bloodstream. During infection, Nm activates C5 and C5a, which also is able to induce TF. We evaluated the effect of eculizumab, a C5-blocking monoclonal antibodies (mAb), on cell-and MP-associated TF. Using a lepirudin-anticoagulated whole blood model, we activated the coagulation and complement cascades by N. meningitidis, and investigated the interaction between the cascade systems with special focus on cell-associated TF-expression (mRNA and protein) and MP-associated TF-dependent thrombin and fibrin generation in platelet-free plasma. We also examined the ability of TF-positive MPs to support clot formation in whole blood. In addition, the effect of corn trypsin inhibitor and timedependent changes on MP-associated functional TF activity was examined. Inhibition of C5 reduced cell-associated TF expression at both gene and protein level, and reduced MP-associated TF-dependent thrombin and fibrin generation in platelet-poor plasma, MP-induced TF-dependent clot formation in whole blood, implying that the complement and coagulation cascades are interplayers in N. meningitidis-mediated activation of these cascades.
引用
收藏
页码:552 / 560
页数:9
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