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A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.
Yang, Aizhen; Zhou, Junsong; Wang, Bo; Dai, Jihong; Colman, Robert W; Song, Wenchao; Wu, Yi.
Afiliação
  • Yang A; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Zhou J; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Wang B; The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
  • Dai J; Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
  • Colman RW; The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
  • Song W; Department of Pathology and Laboratory Medicine, Rutgers-New Jersey Medical School, Newark, New Jersey, USA.
  • Wu Y; The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
FASEB J ; 31(12): 5419-5431, 2017 12.
Article em En | MEDLINE | ID: mdl-28808141
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis. In a K/BxN serum transfer-induced arthritis (STIA) model, mice that lacked HK, pKal, or bradykinin receptors displayed protective phenotypes in joint swelling, histologic changes in inflammation, and cytokine production; however, FXII-deficient mice developed normal arthritis. Inhibition of Kal ameliorated arthritis severity and incidence at early stage STIA and reduced the levels of major cytokines in joints. In addition to releasing bradykinin from HK, Kal directly activated monocytes to produce proinflammatory cytokines, up-regulated their C5aR and FcRIII expression, and released C5a. Immune complex increased pKal activity, which led to HK cleavage. The absence of HK is associated with a decrease in joint vasopermeability. Thus, we identify a critical role for Kal in autoantibody-induced arthritis with pleiotropic effects, which suggests that it is a new target for the inhibition of arthritis.-Yang, A., Zhou, J., Wang, B., Dai, J., Colman, R. W., Song, W., Wu, Y. A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite / Autoanticorpos / Calicreína Plasmática Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite / Autoanticorpos / Calicreína Plasmática Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: FASEB J Assunto da revista: BIOLOGIA / FISIOLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: China