Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis.

摘要: To study the role of stress-induced “readthrough” acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR). Increased AChE hydrolytic activity peripheral blood TgR was associated with increased thrombopoietin levels and platelet counts. Bone marrow (BM) progenitor cells from presented an elevated capacity to produce mixed (GEMM) megakaryocyte (Mk) colonies, which showed intensified labeling its interacting proteins RACK1 PKC. When injected bacterial lipopolysaccharide (LPS), parent strain FVB/N mice, but not reduced Therefore, primed CD34 synthetic ARP26 peptide, derived cleavable C-terminus prior transplantation, into sublethally irradiated NOD/SCID mice. Engraftment (both CD45 CD41 Mk) significantly that received ARP26-primed versus fresh nonprimed cells. Moreover, induced polyploidization proplatelet shedding MEG-01 promegakaryotic cells, engraftment following ex vivo expansion ARP26-treated as compared expanded stem cell factor. Our findings implicate thrombopoietic recovery, suggesting new therapeutic modalities for supporting production. (Blood. 2006;107:3397-3406)