title: Endosomal Redox Signaling in the Antiphospholipid Syndrome.
abstract: OBJECTIVE
  It is well established that the antiphospholipid syndrome (APS) is caused by antiphospholipid antibodies (aPL). While several underlying mechanisms have been described in the past, many open questions remain. Here, we will review data on endosomal signaling and, in particular, redox signaling in APS.
  
  
  RESULTS
  Endosomal redox signaling has been implicated in several cellular processes including signaling of proinflammatory cytokines. We have shown that certain aPL can activate endosomal NADPH-oxidase (NOX) in several cell types followed by induction of proinflammatory and procoagulant cellular responses in vitro. Involvement of endosomes in aPL signaling has also been reported by others. In wild-type mice but not in NOX-deficient mice, aPL accelerate venous thrombus formation underscoring the relevance of endosomal NOX. Furthermore, hydroxychloroquine (HCQ) inhibits activation of endosomal NOX and prevents thrombus formation in aPL-treated mice. Endosomal redox signaling is an important novel mechanism involved in APS pathogenesis. This makes endosomes a potential target for future treatment approaches of APS.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131, Mainz, Germany. karl.lackner@unimedizin-mainz.de.|Center for Translational Vascular Biology, University Medical Center Mainz, Mainz, Germany. karl.lackner@unimedizin-mainz.de.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131, Mainz, Germany.|Center for Translational Vascular Biology, University Medical Center Mainz, Mainz, Germany.|Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors.forename: Davit
authors.initials: D
authors.lastname: Manukyan
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131, Mainz, Germany.|Center for Translational Vascular Biology, University Medical Center Mainz, Mainz, Germany.|Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Müller-Calleja
mesh_terms: D000818:Animals; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000378:metabolism*; D011992:Endosomes / Q000502:physiology*; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology; D020246:Venous Thrombosis / Q000378:metabolism
chemical_list: D019255:NADPH Oxidases
keywords: Antiphospholipid antibodies; Antiphospholipid syndrome; Endosomes; Hydroxychloroquine; NADPH-oxidase; Signal transduction