Section 1 Neutrophils

**3**

mature neutrophils.

**Chapter 1**

*Ota Fuchs*

**1. Development of neutrophils**

Introductory Chapter:

Development of Neutrophils

Microenvironment Regulation

HSCs, including cell adhesion, survival, and cell division [2].

**1.1 The generation of committed proliferative neutrophil precursors**

During the development, HSCs lose their self-renewal potential and produce multipotent precursors (MMPs). All blood cell lineages can be developed from MMPs (**Figure 1**). The differentiation of MMPs into erythro-myeloid or lymphomyeloid progenitors is directed by the antagonistic transcription factors GATA-1 and PU.1. High levels of PU.1 are important for the differentiation of MMPs into lympho-myeloid precursors (LMPs), progenitors for granulocyte-monocyte precursors (GMPs). The most important regulator of physiological granulopoiesis are granulocyte colony-stimulating factor (G-CSF) and its receptor whose effects include commitment of progenitor cells to the myeloid lineage, proliferation and differentiation of granulocytic precursors, release of mature neutrophils from the bone marrow, and modulation of their phagocyte function [3]. Neutrophils carry high levels of G-CSF receptor on their surface through their development and also in mature neutrophils. Humans deficient in G-CSF or its receptor have neutropenia. Interleukin (IL)-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 also stimulate granulopoiesis but are not essential [3]. The transcription factor family of CCAAT enhancer-binding proteins (C/EBPs) is involved in neutrophil development. Granulocytes and macrophages differentiate from the common GMPs [4–6]. Three neutrophil subgroups were identified within the bone marrow by mass cytometry and cell cycle-based analysis [4]. Committed proliferative neutrophil precursors differentiate into nonproliferating immature neutrophils and

and Their Role in Hematopoietic

Neutrophils are the most abundant white blood cells and play a key role in the elimination of pathogens (invading microorganisms). These specialized innate immune cells are a type of polymorphonuclear leukocyte. Humans produce about 1010 to 1011 neutrophils daily in the bone marrow from myeloid precursors in a process known as granulopoiesis. The initial precursors of neutrophils are hematopoietic stem cells (HSCs) [1]. The majority of adult blood and immune cells are derived from HSCs, which are also capable of generating new HSCs in a process called self-renewal. The interaction of HSCs with their particular microenvironments, known as niches, is important for maintaining the stem cell properties of
