Current insights into neutrophil homeostasis.
Neutrophil granulocytes represent the first immunologic barrier against invading pathogens, and neutropenia predisposes to infection. However, neutrophils may also cause significant collateral inflammatory damage. Therefore, neutrophil numbers are tightly regulated by an incompletely understood homeostatic feedback loop adjusting the marrow's supply to peripheral needs. Granulocyte colony-stimulating factor (G-CSF) is accepted to be the major determinant of neutrophil production, and G-CSF levels have, soon after its discovery, been described to be inversely correlated with neutrophil counts. A neutrophil sensor, or "neutrostat," has, therefore, been postulated. The prevailing feedback hypothesis was established in adhesion molecule-deficient mice; it includes macrophages and Th17 cells, which determine G-CSF levels in response to the number of peripherally transmigrated, apoptosing neutrophils. Recent work has deepened our understanding of homeostatic regulation of neutrophil granulopoiesis, but there are still inconsistent findings and unresolved questions when it comes to a plausible hypothesis, similar to the feedback control models of red cell or platelet homeostasis.
Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmology, University Hospital of Tübingen, Tübingen, Germany.
Stefanie
S
Bugl
Stefan
S
Wirths
Martin R
MR
Müller
Markus P
MP
Radsak
Hans-Georg
HG
Kopp
D000818:Animals; D002454:Cell Differentiation; D025461:Feedback, Physiological; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D038042:Myelopoiesis; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor