Chemokines in Trafficking of Hematopoietic Stem and Progenitor Cells and Hematopoiesis

Abstract

Chemokines regulate the process of hematopoiesis by controlling trafficking, proliferation/survival, and differentiation of hematopoietic stem and progenitor cells. Unique expression of the chemokine receptor CXCR4 in combination with adhesion molecules [very late antigen (VLA)-4, lymphocyte function-associated antigen-1 (LFA-1), and VLA-5] on early hematopoietic stem and progenitor cells makes their homing to bone marrow and seeding the stem cell niche possible. In bone marrow, the CXCL12-CXCR4 chemokine axis promotes the survival and retention of hematopoietic stem and early progenitor cells. In certain conditions, hematopoietic stem and progenitor cells are released from bone marrow to the blood circulation, a process called mobilization. Many agents that mobilize marrow progenitor cells induce or activate certain proteases of neutrophils. This leads to degradation of CXCL12 and, therefore, weakens the chemotactic activity of bone marrow. Whereas CXCL12 plays a positive role in survival and proliferation of hematopoietic stem and progenitor cells, many other chemokines suppress these processes. During their differentiation into mature cells, hematopoietic progenitor cells upregulate cell lineage-specific chemokine receptors to migrate to appropriate tissue sites. This cell type-specific switch in chemokine receptors and adhesion molecules is important for tissue-specific migration of hematopoietic cells, a process important for their differentiation or effector function in the periphery.