Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-6280
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dc.contributor.authorDöhrmann, Mareike-
dc.contributor.authorMakhoul, Stephanie-
dc.contributor.authorGross, Kathrin-
dc.contributor.authorKrause, Manuela-
dc.contributor.authorPillitteri, Daniele-
dc.contributor.authorAuer, Charis von-
dc.contributor.authorWalter, Ulrich-
dc.contributor.authorLutz, Jens-
dc.contributor.authorVolf, Ivo-
dc.contributor.authorKehrel, Beate E.-
dc.contributor.authorKerstin, Jurk-
dc.date.accessioned2021-08-16T07:43:13Z-
dc.date.available2021-08-16T07:43:13Z-
dc.date.issued2020-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/6290-
dc.description.abstractThrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with congenital function defects, blocking antibodies, pharmacological inhibitors, and factor-depleted plasma, CD36-sensitive thrombin generation was dependent on FXI, fibrin, and platelet signaling via GPIbα and SFKs. CD36-deficiency or blocking suppressed thrombin-induced platelet αIIbβ3 activation, granule exocytosis, binding of adhesion proteins and FV, FVIII, FIX, FX, but not anionic phospholipid exposure determined by flow cytometry. CD36 ligated specifically soluble fibrin, which recruited distinct coagulation factors via thiols. Selected patients with CKD showed elevated soluble fibrin plasma levels and enhanced thrombin-induced thrombin generation, which was normalized by CD36 blocking. Thus, CD36 is an important amplifier of platelet-dependent thrombin generation when exposure of anionic phospholipids is limited. This pathway might contribute to hypercoagulability in CKD.en_GB
dc.language.isoengde
dc.rightsCC BY-NC*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/*
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleCD36-fibrin interaction propagates FXI-dependent thrombin generation of human plateletsen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-6280-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 04 Medizinde
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleThe FASEB journalde
jgu.journal.volume34de
jgu.journal.issue7de
jgu.pages.start9337de
jgu.pages.end9357de
jgu.publisher.year2020-
jgu.publisher.nameWileyde
jgu.publisher.placeHoboken, NJde
jgu.publisher.urihttps://doi.org/10.1096/fj.201903189Rde
jgu.publisher.issn1530-6860de
jgu.organisation.placeMainz-
jgu.subject.ddccode610de
jgu.publisher.doi10.1096/fj.201903189R
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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