Chapter 121 Neutrophils
The Phagocytic Inflammatory Response
The phagocyte system includes both granulocytes (neutrophils, eosinophils, and basophils) and mononuclear phagocytes (monocytes and tissue macrophages). Neutrophils and mononuclear phagocytes share primary functions, including the defining properties of large particle ingestion and microbial killing. Phagocytes participate primarily in the innate immune response but also help initiate acquired immunity. Mononuclear phagocytes, including tissue macrophages and circulating monocytes, are discussed in Chapter 122.
Neutrophils provide the rapid effector arm of the innate immune system. They circulate in the bloodstream for only about 6 hr (Table 121-1), but upon encountering specific chemotactic signals, they adhere to the vascular endothelium and transmigrate into tissues, where they ingest and kill microbes and release chemotactic signals to recruit more neutrophils and to attract dendritic cells and other initiators of the acquired immune response.
| NEUTROPHILS | |
| Average time in mitosis (myeloblast to myelocyte) | 7-9 day |
| Average time in postmitosis and storage (metamyelocyte to neutrophil) | 3-7 day |
| Average half-life in the circulation | 6 hr |
| Average total body pool | 6.5 × 108 cells/kg |
| Average circulating pool | 3.2 × 108 cells/kg |
| Average marginating pool | 3.3 × 108 cells/kg |
| Average daily turnover rate | 1.8 × 108 cells/kg |
| MONONUCLEAR PHAGOCYTES | |
| Average time in mitosis | 30-48 hr |
| Average half-life in the circulation | 36-104 hr |
| Average circulating pool (monocytes) | 1.8 × 107 cells/kg |
| Average daily turnover rate | 1.8 × 109 cells/kg |
| Average survival in tissues (macrophages) | Months |
From Boxer LA: Function of neutrophils and mononuclear phagocytes. In Bennett JC, Plum F, editors: Cecil textbook of internal medicine, ed 20, Philadelphia, 1996, WB Saunders.
Hematopoiesis
The hematopoietic progenitor system can be envisioned as a continuum of functional compartments with the most primitive compartment composed of very rare pluripotential stem cells, which have high self-renewal capacity and give rise to more mature stem cells, including cells that are committed to either lymphoid or myeloid development (Fig. 121-1). Common lymphoid progenitor cells give rise to T- and B-cell precursors and their mature progeny (Chapter 117). Common myeloid progenitor cells eventually give rise to committed single-lineage progenitors of the recognizable precursors through a random process of lineage restriction in a stepwise process (Chapter 440). The capacity of lineage-specific committed progenitors to proliferate and differentiate in response to demand provides the hematopoietic system with a remarkable range of response to changing requirements for mature blood cell production.
The proliferation, differentiation, and survival of immature hematopoietic progenitor cells are governed by hematopoietic growth factors (HGFs), a family of glycoproteins (Chapter 440). Besides regulating proliferation and differentiation of progenitors, these factors influence the survival and function of mature blood cells. During granulopoiesis and monopoiesis, multiple cytokines regulate the cells at each stage of differentiation from pluripotent stem cells to nondividing terminally differentiated cells (monocytes, neutrophils, eosinophils, and basophils). As cells mature, they lose receptors for most cytokines, especially those that influence early cell development; however, they retain receptors for cytokines that affect their mobilization and function, such as granulocyte colony–stimulating factor (G-CSF) and macrophage colony–stimulating factor (M-CSF). Mature phagocytes also express receptors for chemokines, which help direct the cells to sites of inflammation. Chemokine receptors such as CXCR4 and its ligand SDF-1 play a key role in retention of developing myeloid cells within bone marrow.
