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Macrophage migration inhibitory factor limits activation-induced apoptosis of platelets via CXCR7-dependent Akt signaling.
Chatterjee, Madhumita; Borst, Oliver; Walker, Britta; Fotinos, Anna; Vogel, Sebastian; Seizer, Peter; Mack, Andreas; Alampour-Rajabi, Setareh; Rath, Dominik; Geisler, Tobias; Lang, Florian; Langer, Harald F; Bernhagen, Jürgen; Gawaz, Meinrad.
Afiliação
  • Chatterjee M; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Borst O; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Walker B; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Fotinos A; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Vogel S; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Seizer P; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Mack A; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Alampour-Rajabi S; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Rath D; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Geisler T; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Lang F; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Langer HF; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Bernhagen J; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
  • Gawaz M; From the Medizinische Klinik III, Kardiologie und Kreislauferkrankungen (M.C., O.B., A.F., S.V., P.S., D.R., T.G., H.F.L., M.G.), Institute of Anatomy (A.M.), and Institute of Physiology (B.W., F.L.), Universität Tübingen, Tübingen, Germany; and Institute of Biochemistry and Molecular Cell Biology,
Circ Res ; 115(11): 939-49, 2014 Nov 07.
Article em En | MEDLINE | ID: mdl-25266363
ABSTRACT
RATIONALE Macrophage migration inhibitory factor (MIF) is released on platelet activation. Circulating MIF could potentially regulate platelets and thereby platelet-mediated inflammatory and regenerative mechanisms. However, the effect of MIF on platelets is unknown.

OBJECTIVE:

The present study evaluated MIF in regulating platelet survival and thrombotic potential. METHODS AND

RESULTS:

MIF interacted with CXCR4-CXCR7 on platelets, defining CXCR7 as a hitherto unrecognized receptor for MIF on platelets. MIF internalized CXCR4, but unlike CXCL12 (SDF-1α), it did not phosphorylate Erk1/2 after CXCR4 ligation because of the lack of CD74 and failed in subsequent CXCR7 externalization. MIF did not alter the activation status of platelets. However, MIF rescued platelets from activation and BH3 mimetic ABT-737-induced apoptosis in vitro via CXCR7 and enhanced circulating platelet survival when administered in vivo. The antiapoptotic effect of MIF was absent in Cxcr7(-/-) murine embryonic cells but pronounced in CXCR7-transfected Madin-Darby canine kidney cells. This prosurvival effect was attributed to the MIF-CXCR7-initiated PI3K-Akt pathway. MIF induced CXCR7-Akt-dependent phosphorylation of BCL-2 antagonist of cell death (BAD) both in vitro and in vivo. Consequentially, MIF failed to rescue Akt(-/-) platelets from thrombin-induced apoptosis when challenged ex vivo, also in prolonging platelet survival and in inducing BAD phosphorylation among Akt(-/-) mice in vivo. MIF reduced thrombus formation under arterial flow conditions in vitro and retarded thrombotic occlusion after FeCl3-induced arterial injury in vivo, an effect mediated through CXCR7.

CONCLUSION:

MIF interaction with CXCR7 modulates platelet survival and thrombotic potential both in vitro and in vivo and thus could regulate thrombosis and inflammation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plaquetas / Fatores Inibidores da Migração de Macrófagos / Apoptose / Sistema de Sinalização das MAP Quinases / Proteínas Proto-Oncogênicas c-akt / Receptores CXCR Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plaquetas / Fatores Inibidores da Migração de Macrófagos / Apoptose / Sistema de Sinalização das MAP Quinases / Proteínas Proto-Oncogênicas c-akt / Receptores CXCR Limite: Animals / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article