TY - JOUR
T1 - Elevated levels of full-length and thrombin-cleaved osteopontin during acute dengue virus infection are associated with coagulation abnormalities
AU - Chagan-Yasutan, Haorile
AU - Lacuesta, Talitha Lea
AU - Ndhlovu, Lishomwa C.
AU - Oguma, Shigeru
AU - Leano, Prisca Susan A.
AU - Telan, Elizabeth Freda O.
AU - Kubo, Toru
AU - Morita, Kouichi
AU - Uede, Toshimitsu
AU - Dimaano, Efren M.
AU - Hattori, Toshio
N1 - Funding Information:
This study was supported by the Ministry of Education, Science and Culture (Grants-in-Aid for Scientific Research: Fundamental Research A, Grant Number 23256004 , Overseas Academic Investigation) and a special research grant from the International Research Institute of Disaster Science of Tohoku University (IRIDeS) . The work was also in part supported by the grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (MEXT) for the Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University and National Institute on Minority Health and Health Disparities ( U54MD007584 ), National Institutes of Health (NIH). We would like to thank all the patients and volunteers who participated in this study.
PY - 2014
Y1 - 2014
N2 - Introduction Dengue virus (DENV) is transmitted by the mosquito vector, and causes a wide range of symptoms that lead to dengue fever (DF) or life-threatening dengue hemorrhagic fever (DHF). The host and viral correlates that contribute to DF and DHF are complex and poorly understood, but appear to be linked to inflammation and impaired coagulation. Full-length osteopontin (FL-OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN, integrate multiple immunological signals through the induction of pro-inflammatory cytokines. Materials and Method To understand the role of OPN in DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin [TM], and ferritin in blood obtained from 65 DENV infected patients in the critical and recovery phases of DF and DHF during a dengue virus epidemic in the Philippines in 2010. Results Levels of FL-OPN, trOPN, D-dimer, TAT, and TM were significantly elevated in the critical phase in both the DF and DHF groups, as compared with healthy controls. During the recovery phase, FL-OPN levels declined while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN levels were directly correlated with D-dimer and ferritin levels, while the generation of trOPN was associated with TAT levels, platelet counts, and viral RNA load. Conclusion Our study demonstrated the marked elevation of plasma levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for the first time. Further studies on the biological functions of these matricellular proteins in DENV-infection would clarify its pathogenesis.
AB - Introduction Dengue virus (DENV) is transmitted by the mosquito vector, and causes a wide range of symptoms that lead to dengue fever (DF) or life-threatening dengue hemorrhagic fever (DHF). The host and viral correlates that contribute to DF and DHF are complex and poorly understood, but appear to be linked to inflammation and impaired coagulation. Full-length osteopontin (FL-OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN, integrate multiple immunological signals through the induction of pro-inflammatory cytokines. Materials and Method To understand the role of OPN in DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin [TM], and ferritin in blood obtained from 65 DENV infected patients in the critical and recovery phases of DF and DHF during a dengue virus epidemic in the Philippines in 2010. Results Levels of FL-OPN, trOPN, D-dimer, TAT, and TM were significantly elevated in the critical phase in both the DF and DHF groups, as compared with healthy controls. During the recovery phase, FL-OPN levels declined while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN levels were directly correlated with D-dimer and ferritin levels, while the generation of trOPN was associated with TAT levels, platelet counts, and viral RNA load. Conclusion Our study demonstrated the marked elevation of plasma levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for the first time. Further studies on the biological functions of these matricellular proteins in DENV-infection would clarify its pathogenesis.
KW - Coagulation
KW - Dengue virus
KW - Full-length osteopontin
KW - Inflammation
KW - Thrombin
KW - Thrombin-cleaved osteopontin
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U2 - 10.1016/j.thromres.2014.05.003
DO - 10.1016/j.thromres.2014.05.003
M3 - Article
C2 - 24861695
AN - SCOPUS:84905093713
VL - 134
SP - 449
EP - 454
JO - Thrombosis Research
JF - Thrombosis Research
SN - 0049-3848
IS - 2
ER -