Regulation of neutrophil homeostasis.
OBJECTIVE
Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil number in the blood is tightly regulated. Herein, we review recent studies that have greatly advanced our understanding of the mechanisms controlling neutrophil homeostasis.


RESULTS
Accumulating evidence shows that stromal derived factor-1 (CXCL12) through interaction with its major receptor CXCR4 provides a key retention signal for neutrophils in the bone marrow. Granulocyte colony-stimulating factor induces neutrophil release from the bone marrow, in major part, by disrupting stromal derived factor-1/CXCR4 signaling. Granulocyte colony-stimulating factor expression is regulated by a novel feedback loop that senses neutrophil emigration into tissues. Specifically, engulfment of apoptotic neutrophils by tissue phagocytes initiates a cytokine cascade that includes interleukin-23, interleukin-17, and ultimately granulocyte colony-stimulating factor.


CONCLUSIONS
Granulocyte colony-stimulating factor plays a central role in the dynamic regulation of neutrophil production and release from the bone marrow in response to environmental stresses. Recent studies have begun to elucidate both the pathways linking neutrophil clearance to granulocyte colony-stimulating factor expression and the mechanisms by which the factor induces neutrophil release from the bone marrow. These studies may lead to novel strategies to modulate neutrophil responses in host defense and inflammation.
Christopher
Matthew J
MJ
Division of Oncology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Link
Daniel C
DC
D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D009504:Neutrophils / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor