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dc.contributor.authorRudolph, Jochen Michael
dc.contributor.authorGuttek, Karina
dc.contributor.authorWeitz, Gabriele
dc.contributor.authorMeinke, Clara Antonia
dc.contributor.authorKliche, Stefanie
dc.contributor.authorReinhold, Dirk
dc.contributor.authorSchraven, Burkhart
dc.contributor.authorReinhold, Annegret
dc.description.abstractThe adhesion and degranulation-promoting adapter protein (ADAP) is expressed in T cells, NK cells, myeloid cells, and platelets. The involvement of ADAP in the regulation of receptor-mediated inside-out signaling leading to integrin activation is well characterized, especially in T cells and in platelets. Due to the fact that animal studies using conventional knock-out mice are limited by the overlapping effects of the different ADAP-expressing cells, we generated conditional ADAP knock-out mice (ADAPfl/fl PF4-Cretg). We observed that loss of ADAP restricted to the megakaryocytic lineage has no impact on other hematopoietic cells even after stimulation conditions. ADAPfl/fl PF4-Cretg mice showed thrombocytopenia in combination with reduced plasma levels of PF4 and TGF-β1. In vitro, platelets from these mice revealed reduced P-selectin expression, lower TGF-β1 release, diminished integrin αIIbβ3 activation and decreased fibrinogen binding after stimulation with podoplanin, the ligand of the C-type lectin-like receptor-2 (CLEC-2). Furthermore, loss of ADAP was associated with impaired CLEC-2-mediated activation of PLCγ2 and Erk1/2. Induction of experimental autoimmune encephalomyelitis (EAE) in mice lacking ADAP expression in platelets caused a more severe disease. In vivo administration of TGF-β1 early after T cell transfer improved EAE severity in mice with loss of ADAP restricted to platelets. Our results reveal a regulatory function of ADAP in platelets in vitro and during autoimmune disease EAE in vivo.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.titleCharacterization of mice with a platelet-specific deletion of the adapter molecule ADAP.en_US
dc.contributor.departmentHZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.en_US
dc.identifier.journalMolecular and Cellular Biologyen_US
dc.source.journaltitleMolecular and cellular biology

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