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Impaired erythropoiesis after haemorrhagic shock in mice is associated with erythroid progenitor apoptosis in vivo
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
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2008 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 5, 605-13 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Multiply traumatised patients often suffer from blood loss and from subsequent therapy-resistant anaemia, possibly mediated by apoptosis, necrosis, or humoral factors. Therefore, the underlying mechanisms were investigated in bone marrow (BM) and peripheral blood in a murine resuscitated haemorrhagic shock (HS) model. METHODS: In healthy male mice, pressure-controlled HS was induced for 60 min. The BM was analysed for Annexin-V, 7-amino-actinomycin D, apoptotic enzymes (caspases-3/7, -8, and -9), expression of death receptors (CD120a, CD95), mitochondrial proteins (Bax, Bcl-2, Bcl-x), as well as erythropoietin (EPO) receptor (EPO-R). Blood cell count, peripheral EPO, and tumour necrosis factor-alpha response were additionally monitored. RESULTS: Twenty-four and 72 h after HS, EPO and EPO-R were strongly up-regulated in peripheral blood and BM, respectively. Decreasing numbers of erythroid progenitors in BM after HS correlated with significant apoptotic changes confirmed by increased caspases-3/7, -8, -9 activity in total BM, death receptor CD95 and CD120a expression on erythroid progenitors, and down-regulated mitochondrial Bcl-2 expression in total BM. Erythroid progenitors in peripheral blood were found to be increased after 72 h. CONCLUSION: Despite the massive EPO response and up-regulation of EPO-R, BM erythroblasts (EBs) decreased. This could be due to deficient maturation of erythroid progenitors. Furthermore, the increased intrinsic and extrinsic apoptosis activation suggests programmed death of erythroid progenitors. We propose that both apoptosis and negatively regulated erythropoiesis contribute to BM dysfunction, while erythroid progenitor egress plays an additional role.

Place, publisher, year, edition, pages
2008. Vol. 52, no 5, 605-13 p.
Keyword [en]
Erythropoiesis, haemorrhage, erythropoietin, erythroid progenitors
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URN: urn:nbn:se:uu:diva-113120DOI: 10.1111/j.1399-6576.2008.01656.xPubMedID: 18419713OAI: oai:DiVA.org:uu-113120DiVA: diva2:289830
Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2010-04-21Bibliographically approved

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