Annexin-2 is a regulator of stromal cell-derived factor-1/CXCL12 function in the hematopoietic stem cell endosteal niche

作者：Jung Younghun; Shiozawa Yusuke; Wang Jingcheng; Patel Lalit R; Havens Aaron M; Song Junhui; Kreb**ach Paul H; Roodman G David; Taichman Russell S^*

来源：Experimental Hematology, 2011, 39(2): 151-166.

DOI：10.1016/j.exphem.2010.11.007

Objective. Previously, we reported that annexin-2 (anxa2) plays an important role in hematopoietic stem cell (HSC) localization to the endosteal/osteoblastic marrow niche. This study explored the role that annexin-2 plays in presenting stromal cell-derived factor - 1 (or CXCL12) to HSCs.
Materials and Methods. Competitive long-term bone marrow transplant assays were used to determine if HSC engraftment is altered in annexin-2 - deficient animals. Colony-forming cell assays, CXCL12 enzyme-linked immunosorbent assay, and real-time reverse transcription polymerase chain reaction analyses were used to determine stem or progenitor cell mobilization by granulocyte colony-stimulating factor. Immunohistochemistry, immunoprecipitation, binding assays, and chemotactic assays were employed to determine if annexin-2 is associated with CXCL12. Degradation assays were also used to determine if annexin-2 and CXCL12 protect each other from proteolytic degradation.
Results. Anxa2(-/-) animals had fewer HSCs in their marrow, and the HSCs in anxa2(-/-) animals express less CXCR4 and CXCR7, suggesting a cell intrinsic defect. Transplantation studies of wild-type marrow into anxa2(-/-) animals demonstrated a cell-extrinsic defect in the anxa2(-/-) animals. CXCL12 binds directly to annexin-2, and this interaction facilitates presentation of CXCL12 to HSCs. Yet the binding of CXCL12 to annexin-2 did not protect CXCL12 from proteolytic cleavage after stem or progenitor cell mobilization by granulocyte colony-stimulating factor.
Conclusions. These results suggest that annexin-2 serves as an anchor for CXCL12 to help in the localization of HSCs to the niche.

• 出版日期2011-2