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Dengue virus-induced autoantibodies bind to plasminogen and enhance its activation.
J Immunol. 2011 Dec 15; 187(12):6483-90.JI

Abstract

Dengue virus infection can lead to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in patients. Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks associated with DHF/DSS patients. However, the mechanisms that cause pathology in DHF/DSS patients are still unclear. Because conversion of plasminogen (Plg) to plasmin (Plm) is the first step in the activation of fibrinolysis, Abs against Plg found in DHF/DSS patients may be important. Therefore, to investigate the specificity, function, and possible origin of these Abs, we generated several Plg cross-reactive mAbs from DENV-immunized mice. An IgG mAb, 6H11, which recognizes an epitope associated with a dengue envelope protein, demonstrated a high level of cross-reactivity with Plg. The 6H11 Ab was further characterized with regard to its effect on Plg activation. Using Plm-specific chromogenic substrate S-2251, we found that mAb 6H11 demonstrated serine protease activity and could convert Plg directly to Plm. The serine protease activity of mAb 6H11 was further confirmed using serine protease chromogenic substrate S-2288. In addition, we found several Plg cross-reactive mAbs that could enhance urokinase-induced Plg activation. Lastly, mAb 6H11 could induce Plm activity and increase the level of D-dimer (a fibrin degradation product) in both human and mouse platelet-poor plasma. Taken together, these data suggest DENV-induced Plg cross-reactive Abs may enhance Plg conversion to Plm, which would be expected to contribute to hyperfibrinolysis in DHF/DSS patients.

Authors+Show Affiliations

Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan 701.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22079981

Citation

Chuang, Yung-Chun, et al. "Dengue Virus-induced Autoantibodies Bind to Plasminogen and Enhance Its Activation." Journal of Immunology (Baltimore, Md. : 1950), vol. 187, no. 12, 2011, pp. 6483-90.
Chuang YC, Lei HY, Lin YS, et al. Dengue virus-induced autoantibodies bind to plasminogen and enhance its activation. J Immunol. 2011;187(12):6483-90.
Chuang, Y. C., Lei, H. Y., Lin, Y. S., Liu, H. S., Wu, H. L., & Yeh, T. M. (2011). Dengue virus-induced autoantibodies bind to plasminogen and enhance its activation. Journal of Immunology (Baltimore, Md. : 1950), 187(12), 6483-90. https://doi.org/10.4049/jimmunol.1102218
Chuang YC, et al. Dengue Virus-induced Autoantibodies Bind to Plasminogen and Enhance Its Activation. J Immunol. 2011 Dec 15;187(12):6483-90. PubMed PMID: 22079981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dengue virus-induced autoantibodies bind to plasminogen and enhance its activation. AU - Chuang,Yung-Chun, AU - Lei,Huan-Yao, AU - Lin,Yee-Shin, AU - Liu,Hsiao-Sheng, AU - Wu,Hua-Lin, AU - Yeh,Trai-Ming, Y1 - 2011/11/11/ PY - 2011/11/15/entrez PY - 2011/11/15/pubmed PY - 2012/2/9/medline SP - 6483 EP - 90 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 187 IS - 12 N2 - Dengue virus infection can lead to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in patients. Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks associated with DHF/DSS patients. However, the mechanisms that cause pathology in DHF/DSS patients are still unclear. Because conversion of plasminogen (Plg) to plasmin (Plm) is the first step in the activation of fibrinolysis, Abs against Plg found in DHF/DSS patients may be important. Therefore, to investigate the specificity, function, and possible origin of these Abs, we generated several Plg cross-reactive mAbs from DENV-immunized mice. An IgG mAb, 6H11, which recognizes an epitope associated with a dengue envelope protein, demonstrated a high level of cross-reactivity with Plg. The 6H11 Ab was further characterized with regard to its effect on Plg activation. Using Plm-specific chromogenic substrate S-2251, we found that mAb 6H11 demonstrated serine protease activity and could convert Plg directly to Plm. The serine protease activity of mAb 6H11 was further confirmed using serine protease chromogenic substrate S-2288. In addition, we found several Plg cross-reactive mAbs that could enhance urokinase-induced Plg activation. Lastly, mAb 6H11 could induce Plm activity and increase the level of D-dimer (a fibrin degradation product) in both human and mouse platelet-poor plasma. Taken together, these data suggest DENV-induced Plg cross-reactive Abs may enhance Plg conversion to Plm, which would be expected to contribute to hyperfibrinolysis in DHF/DSS patients. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/22079981/Dengue_virus_induced_autoantibodies_bind_to_plasminogen_and_enhance_its_activation_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=22079981 DB - PRIME DP - Unbound Medicine ER -