Neutrophil Biology and the Next Generation of Myeloid Growth Factors

Abstract

Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections. The bone marrow must produce approximately 10 × 109 neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid grow factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay their renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community. In Europe these products are called bio-similars. Throughout the world, new version and copied version of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of the myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.

Polyphenol E Enhances the Antitumor Immune Response in Neuroblastoma by Inactivating Myeloid Suppressor Cells

“…S6A). We focused our attention on G-CSF and IL-6, as these cytokines were previously shown to be important for the differentiation and proliferation of myeloid cells (16,17). We validated the Polyphenon E-induced secretion of the G-CSF and IL-6 by ELISA (not shown).…”

Mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils

“…These pseudopods were not observed when neutrophils were added to hCMEC/D3 that were not exposed to DOXO or EFIG-AM and therefore did not exhibit formation of barrier bodies. Pseudopod formation by neutrophils was described as the first step in neutrophil phagocytosis ( 30 , 31 ). The ingestion process of an extracellular Pgp/Pgp substrate vesicle by a nuclear-stained neutrophil is depicted in SI Appendix , Fig.…”

Immunostimulation of Sugar Cane Extract on Neutrophils to Salmonella typhimurium Infection in Mice

“…Both neutrophil migration to the site of infection and increased leukocyte production in the bone marrow are very important in fighting acute bacterial infections. The processes of increasing the generation and maturation of neutrophils are regulated by a panel of cytokines, including stromal cell factor, IL‐1, IL‐3, IL‐6, GM‐CSF and G‐CSF, that is induced by inflammatory stimuli (Dale, ). It takes 60 h for metamyelocytes to develop and 50 to 72 h for these cells to mature into neutrophils, a process in which GM‐CSF and G‐CSF are critically important (Abbas, ).…”