Up-regulated expression of CXCL12 in human spleens with extramedullary haematopoiesis

Aims: To determine the expression of CXCL12 in human spleens with extramedullary haematopoiesis (EMH) for clarifying the association of splenic haematopoietic stem cells (HSCs) with CXCL12, which has been demonstrated to be a marker of bone marrow niches. Methods: We examined the expression of mRNA for CXCL12 by quantitative reverse transcription polymerase chain reaction (RT-PCR) and localised the CXCL12 protein by immunohistochemical staining in EMH negative and positive spleen samples from autopsy cases. Results: Expression of CXCL12 was significantly higher in samples from EMH positive cases than those from EMH negative cases. CXCL12 was localised to the endothelial cells of the sinuses of the red pulp in EMH positive spleens while vascular endothelial cells of the white pulp expressed CXCL12 throughout the spleen. c-kit positive/CD34 negative cells were identified in contact with CXCL12 positive endothelial cells of sinuses in EMH positive cases, although the number was few. In contrast, erythroblastic islands were frequently observed in EMH positive cases and dominantly localised to the intrasinusoidal spaces in association with CD68 positive macrophages. Conclusions: Our results suggest that endothelial cells of splenic sinuses expressing CXCL12 may contribute to attracting circulating haematopoietic precursor cells and constitute bone marrow niche-like regions of EMH in humans. Differentiating haematopoietic cells may move into intrasinusoidal spaces to form EMH foci such as erythroblastic accumulation.