Granulocyte colony-stimulating factor: Molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis

Abstract

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.

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…Similarly, tumor-secreted G-CSF that contributes to neutrophil mobilization, activation and stimulation of oxidative metabolism [188][189][190][191], is also involved in the polarization towards immunosuppressive MDSCs [192,193]. The presence of G-MDSCs was shown to be important for promoting tumor growth [193].…”

Changes in Gene Expression during G-CSF–Induced Emergency Granulopoiesis in Humans

“…mRNA array data were analyzed with Qlucore Omics Explorer version 3.1 (8) for changes in expression between samples from G-CSF-treated donors and G-CSF-naive donors as a result of treatment and the interaction between time and treatment, but excluding time alone, using a two-way ANOVA with pairing of samples according to donor. A q value ,0.001 was considered statistically significant.…”

G-CSF Induces Membrane Expression of a Myeloperoxidase Glycovariant that Operates as an E-selectin Ligand on Human Myeloid Cells

“…Binding of G-CSF to its receptor on early hematopoietic progenitors and on intermediate-stage myeloid progenitors activates proliferation pathways, resulting in programmed expansion and release ("mobilization") of progenitors and mature myeloid cells into the peripheral circulation (2). This cytokine is in routine clinical use, administered to stimulate myelopoiesis after chemo-or radiotherapy, to treat cyclic neutropenia, and to mobilize progenitor cells for hematopoietic stem cell transplantation (HSCT) (3).…”

“…glycosylation | leukemia | hematopoietic stem cell transplantation G ranulocyte-colony stimulating factor (G-CSF) serves a critical role in native immunity by directing elaboration of myeloid cells and their cytocidal arsenal (1), and the characteristic leukocytosis (the "leukemoid reaction") of inflammatory reactions is fueled by physiologic up-regulation of G-CSF (2). Binding of G-CSF to its receptor on early hematopoietic progenitors and on intermediate-stage myeloid progenitors activates proliferation pathways, resulting in programmed expansion and release ("mobilization") of progenitors and mature myeloid cells into the peripheral circulation (2).…”