Dock2 participates in bone marrow lympho-hematopoiesis

• Published in: Biochemical and biophysical research communications Vol. 367; no. 1; pp. 90 - 96
• Main Authors: Kikuchi, Tomoko, Kubonishi, Shiro, Shibakura, Misako, Namba, Noriko, Matsui, Toshimitsu, Fukui, Yoshinori, Tanimoto, Mitsune, Katayama, Yoshio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.02.2008
• Subjects: Actins - metabolism; Animals; Bone Marrow - drug effects; Bone Marrow - metabolism; Bone Marrow - pathology; Bone Marrow Transplantation - pathology; Chemokine CXCL12 - pharmacology; Chemotaxis - physiology; CXCL12; CXCR4; Dock2; Fluorouracil - pharmacology; GTPase-Activating Proteins - pharmacology; Hematopoiesis - drug effects; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Hematopoietic stem/progenitor cells; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Lymphocytes - drug effects; Lymphocytes - metabolism; Lymphocytes - pathology; Mice; Mice, Inbred C57BL; Receptors, CXCR4 - metabolism; Stem Cells - cytology; Stem Cells - metabolism; Stem Cells - pathology; Time Factors; Hematopoietic stem/progenitor cells; CXCR4; CXCL12; Dock2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.12.093

Dock2 has been shown to be indispensable for chemotaxis of mature lymphocytes as a critical Rac activator. However, the functional expression of Dock2 in immature hematopoietic cells is unclear. In this study, we demonstrate that Dock2 is broadly expressed in bone marrow (BM) hematopoietic compartment, including hematopoietic stem/progenitor cell (HSC/HPC) fraction. Response of Dock2−/− HPCs to CXCL12 in chemotaxis and actin polymerization in vitro was impaired, although α4 integrin activation by CXCL12 was not altered. Myelosuppressive stress on HSCs in vivo, such as consecutive 5-FU administration and serial bone marrow transplantation, did not show hematopoietic defect in Dock2−/− mice. Long-term engraftment of transplanted Dock2−/− BM cells was severely impaired in competitive reconstitution. However, this was not intrinsic to HSCs but originated from the defective competition of Dock2−/− lymphoid precursors. These results suggest that Dock2 plays a significant role in BM lymphopoiesis, but is dispensable for HSC engraftment and self-renewal.