[2] Macrophages

originate from circulating peripheral-blood monocytes that differentiate from common myeloid progenitors (CMP) in the bone marrow, which are also the common precursor for neutrophils, eosinophils, basophils, macrophages, DCs and mast cells. The haematopoietic growth factor colony-stimulating factor (CSF)-1 primarily controls the differentiation, maturation and survival of monocytes and macrophages. X-396 In response to CSF-1, monocytes differentiate from CMPs via the granulocyte/macrophage progenitor and macrophage/DC progenitor (MDP). Subsequently, these progenitors give rise to monoblasts, pro-monocytes and ultimately monocytes that are released into the circulation before entering tissues INCB024360 supplier to become resident tissue macrophages. Most

tissues and organs harbour a resident macrophage population that plays an important role in tissue homeostasis from their functional role in phagocytosis and matrix remodelling. However, there is growing evidence that monocytes can also differentiate into DCs depending upon the surrounding tissue microenvironment. This is particularly evident in non-lymphoid organs such as the kidney, where there is considerable phenotypic and functional overlap between macrophage and DC populations. Monocytes represent a heterogeneous population of cells and constitute approximately 10% and 4% of leukocytes in humans and mice, respectively.[3] Monocyte heterogeneity was initially discovered in humans over 20 years ago based on the differential expression of the antigenic markers CD14 and CD16.[4] This enabled the categorization of

human monocytes into three major subsets: CD14hiCD16−, CD14+CD16+ and CD14dimCD16+ cells (Table 1).[4, 5] CD14hiCD16− monocytes PJ34 HCl are referred to as ‘classical’ because their phenotype resembles the original description of monocytes, representing approximately 90% of total peripheral blood monocytes in a healthy person.[4, 6] In contrast, CD14+CD16+ monocytes, termed ‘non-classical’, constitute less than 10% of the total monocyte population and are phenotypically smaller and less dense. In patients with acute inflammation[7] and infectious diseases,[8, 9] monocyte numbers are significantly increased. Consequently, Grage-Griebenow et al.[5] identified an additional CD16+ monocyte population with reduced CD14 expression termed CD14dimCD16+ ‘intermediate’ monocytes. These monocytes represent approximately 5% of total blood monocytes and are functionally distinct from the CD14+CD16+ subset, with low phagocytic activity and high pro-inflammatory cytokine production, particularly tumour necrosis factor-α (TNF-α) and interleukin (IL)-1.