Impact of inflammation on early hematopoiesis and the microenvironment.

Abstract

Steady-state hematopoiesis is maintained by slowly dividing, self-renewing hematopoietic stem cells (HSCs) and their offspring, lineage-specified downstream progenitors in bone marrow (BM). It was previously thought that hematopoietic stresses such as infection or other inflammatory stimuli, are mostly recognized by terminally differentiated immune cells, i.e., front-line defenders at the local site of reaction, and that they produce factors that directly act on hematopoietic stem and progenitors (HSPCs) in BM and subsequently stimulate them to rebuild and sustain the hemato-lymphatic system. However, accumulating evidence now indicates that primitive HSPCs, as well as microenvironmental cells in BM are also able to sense systemically migrating hematopoietic stress signals, and respond by orchestrating on-site hematopoiesis via direct and indirect mechanisms. While inflammation has many beneficial roles in activating the immune system for defense or facilitating tissue repair, it also shows detrimental effects if sustained chronically, i.e., might lead to HSPC damage as bone marrow failure or leukemia. Thus, inflammation requires tight control of initiation and termination in time and space dependent manner.