The ABC of Thrombopoiesis

Abstract

Figure. ABCB6 deficiency stimulates platelet production and promotes atherosclerosis. The lack of ABCB6 in bone marrow cells enhances the production of reactive oxygen species in megakaryocyte progenitors (MkP), thus stimulating megakaryopoiesis. The peripheral increase in circulating platelets is an important factor for the arterial recruitment of myeloid cells because platelets deposit the chemokine CCL5 (RANTES) and activate leukocyte by complexes formation. Overall, these mechanisms stimulate platelet-driven atherosclerosis. ErP indicates erythroid-progenitor cell; and MEP, megakaryocyte-erythroid progenitor cell. thrombopoiesis also under acute inflammatory conditions, one might envision broader targeting approaches in settings of acute inflammation with importance of platelet-derived chemokines such as acute lung injury. 9 Finally, it may also be of interest to test whether the reverse approach, namely the therapeutic inhibition of ABCB6 function, can promote megakaryopoiesis and increase platelet counts in patients with thrombocytopenia. Sources of FundingThe author's research is supported by the NWO (VIDI project 91712303), the DFG (SO876/3-1, SO876/6-1, FOR809, SFB914 TPB08), the Else Kröner Fresenius Stiftung, and the LMUexcellence program of the Ludwig-Maximilians-University Munich. DisclosuresNone. References

Platelets

“…ABCG4 and ABCB6) leads to increased platelet production and atherosclerosis in hypercholesterolemic mice(3, 4). Specifically, the lack of ABCB6 in the bone marrow leads to unrestrained platelet production, enhanced pro-inflammatory platelet activity, and accelerated atherosclerosis in Ldlr −/− mice(4, 5). The significance in this work lies in the possibility for a novel thrombolytic approach in part by tempering the production of reactive platelets.…”

Structural Insights into Porphyrin Recognition by the Human ATP-Binding Cassette Transporter ABCB6

“…It is highly expressed in heart, liver, intestine, testis, skeletal muscle, and skin ( Chavan et al, 2013 ; Krishnamurthy et al, 2006 ; Zhang et al, 2013 ). Mutations of ABCB6 are associated with various genetic diseases including porphyria and dyschromatosis universalis hereditaria (DUH, a disorder of pigment metabolism) ( Zhang et al, 2013 ), pseudohyperkalemia (chronic renal failure) ( Andolfo et al, 2013 ), coloboma (a developmental defect of the eye) ( Wang et al, 2012 ), and atherosclerosis ( Soehnlein, 2014 ). A high level of ABCB6 is also found in red blood cells where its absence defines the Langereis blood group system ( Lan ) ( Helias et al, 2012 ).…”