Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis.
Neutrophils are phagocytes whose principal function is to maintain anti-bacterial immunity. Neutrophils ingest and kill invading bacteria, releasing cytotoxic, chemotactic and inflammatory mediators at sites of infection. This serves to control the immediate host immune response and attract other cells, such as macrophages and dendritic cells, which are important for establishing long-term adaptive immunity. Neutrophils thus contribute to both the initiation and the maintenance of inflammation at sites of infection. Aberrant neutrophil activity is deleterious; suppressed responses can cause extreme susceptibility to infection while overactivation can lead to excessive inflammation and tissue damage. This review will focus on neutrophil regulation by granulocyte colony-stimulating factor (G-CSF), the principal cytokine controlling neutrophil development and function. The review will emphasize the molecular aspects of G-CSF-driven granulopoiesis in steady state (healthy) conditions and during demand-driven or 'emergency' conditions elicited by infection or clinical administration of G-CSF. Understanding the molecular control of granulopoiesis will aid in the development of new approaches designed to treat disorders of neutrophil production and function.
Panopoulos
Athanasia D
AD
Department of Immunology and Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, PO Box 301402, Unit 902, Houston, TX 77030, USA.
Watowich
Stephanie S
SS
D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology; D051379:Mice; D038042:Myelopoiesis / Q000502:physiology*; D009503:Neutropenia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D018375:Neutrophil Activation / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology; D015398:Signal Transduction
D020381:Interleukin-17; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor