**Acknowledgements**

*Cells of the Immune System*

in other niches of the liver and the spleen HSCs.

ence HSC homeostasis and fate.

row [29, 30]. Nestin-positive (Nes+

**stem cell microenvironment**

showed that bone marrow Gr1+

is facilitated by neutrophils [33, 34].

Bone marrow Gr1+

identification of cells which synthesize HSC regulators (CXCL12, CXCL4, stem cell factor (SCF), thrombopoietin, osteopontin, transforming growth factor-β, vascular cell adhesion molecule 1 (VCAM1), glycoprotein 130, Notch ligands such as Jagged-1, fibroblast growth factor 1, angiopoietin-1, and pleiotrophin). Many further factors produced by other tissues can also affect stem cells and their microenvironment. The main site of hematopoiesis in adults is bone marrow. However, in response to severe hematopoietic stresses, extramedullary hematopoiesis was found

In the steady state, 90% of neutrophils reside in the bone marrow, and only 1–2% of neutrophils are present in the circulation [28]. Two neutrophil-derived proteases, cathepsin G and elastase, cleave receptors and cytokines essential for HSC retention in the bone marrow (CXCR4, CXCL1, and VCAM1) and change the HSC-supportive properties of the bone marrow [28]. Further experiments showed that neutrophil-derived proteases are not necessary for HSC mobilization. Macrophages, megakaryocytes, regulatory T cells (Tregs), and neutrophils influ-

A majority of HSCs in the bone marrow localize near the sinusoidal blood vessels. Endothelial cells supply HSCs by CXCL12 and SCF. Both these factors are important for HSCs maintaining within the microenvironment of the bone mar-

constituents in an adult bone marrow. Studies using green fluorescent protein under the direction of nestin promoter/enhancer (*Nes*-GFP) revealed two groups of mesenchymal progenitor cells, one associated with arterioles (bright cells) and one associated with sinusoids (dim cells). The sympathetic nervous system also regulates hematopoietic stem cells in the bone marrow microenvironment [31].

**2.2 Tumor necrosis factor α (TNF α) synthesized by activated bone marrow neutrophils and its role in the regeneration of the damaged hematopoietic** 

Gr1/Ly6G (lymphocyte antigen 6 complex locus G6D) is a 21–25 kD glycosylphosphatidylinositol (GPI)-linked differentiation antigen that is expressed by myeloid-derived cells in a tightly developmentally regulated manner in the bone marrow. CD115 (M-CSF receptor) has been used to define monocytes. Bowers et al.

damaged vascular hematopoietic microenvironment in mice after transplantation [32].

proliferating neutrophil progenitors and immature and mature neutrophils with different transcriptional signatures in comparison with circulating neutrophils [4]. Bone marrow neutrophils are selectively recruited to the damaged sinusoidal vasculature, where they secrete TNFα. This cytokine is a potent inducer of new blood vessel growth (angiogenesis) [32]. The treatments used before transplantation for abolishment of the host hematopoietic cells destroy the bone marrow vascular microenvironment. Donor HSCs increase their proliferation and neutrophils together with other myeloid cell production. Therefore, the hematopoietic progenitor engraftment

**3. Various phenotypes and functions displayed by neutrophils**

Neutrophils are innate immune cells engaged in protection against bacterial, viral, parasitic, and fungal pathogens and in tissue repair [35]. Infected tissues and tissues with sterile stress can be also damaged by the toxic activity of neutrophils [35].

) cells are important hematopoiesis-supporting

CD115<sup>−</sup> neutrophils support the regeneration of the

CD115<sup>−</sup> neutrophils are a heterogenous population which contains

**6**

The work was supported by the research project for conceptual development of research organization (00023736; Institute of Hematology and Blood Transfusion, Prague) from the Ministry of Health of the Czech Republic.
