| First Author | Wysoczynski M | Year | 2007 |
| Journal | Leukemia | Volume | 21 |
| Issue | 5 | Pages | 973-82 |
| PubMed ID | 17330096 | Mgi Jnum | J:121386 |
| Mgi Id | MGI:3709940 | Doi | 10.1038/sj.leu.2404629 |
| Citation | Wysoczynski M, et al. (2007) Cleavage fragments of the third complement component (C3) enhance stromal derived factor-1 (SDF-1)-mediated platelet production during reactive postbleeding thrombocytosis. Leukemia 21(5):973-82 |
| abstractText | We hypothesized that the third complement component (C3) cleavage fragments (C3a and (des-Arg)C3a) are involved in stress/inflammation-related thrombocytosis, and investigated their potential role in reactive thrombocytosis induced by bleeding. We found that platelet counts are lower in C3-deficient mice in response to excessive bleeding as compared to normal littermates and that C3a and (des-Arg)C3a enhance stromal-derived factor-1 (SDF-1)-dependent megakaryocyte (Megs) migration, adhesion and platelet shedding. At the molecular level, C3a stimulates in Megs MAPKp42/44 phosphorylation, and enhances incorporation of CXCR4 into membrane lipid rafts increasing the responsiveness of Megs to SDF-1. We found that perturbation of lipid raft formation by statins decreases SDF-1/C3a-dependent platelet production in vitro and in an in vivo model statins ameliorated post-bleeding thrombocytosis. Thus, inhibition of lipid raft formation could find potential clinical application as a means of ameliorating some forms of thrombocytosis. |
