Originally, monocytes and macrophages were classified as cells of the reticulo-endothelial system - RES (Aschoff, 1924). Van Furth et al. (1972) proposed the mononuclear phagocyte system -- MPS, and monocytes and macrophages became basic cell types of this system. Their development takes in the bone marrow and passes through the following steps: stem cell - committed stem cell - monoblast - promonocyte - monocyte (bone marrow) - monocyte (peripheral blood) - macrophage (tissues). Monocyte differention in the bone marrow proceeds rapidly (1.5 to 3 days). During differentation, granules are formed in monocyte cytoplasma and these can be divided as in neutrophils into at least two types. However, they are fewer and smaller than their neutrophil counterparts (azurophil and specific granules). Their enzyme content is similar.
The process of haematopoiesis is controlled by a group of at
least 11 growth factors. Three of these glycoproteins initiate the
differentiation of macrophages from uni- and bipotential
progenitor cells in the bone marrow. The progression from
pluripotential stem cell to myeloid-restricted progenitor is
controlled by IL-3, which generates differentiated progeny of all
myeloid lineages. As IL-3-responsive progenitors differentiate,
they became responsive to GM-CSF and M-CSF, the two growth factors
giving rise to monocyte/macrophage-restricted progeny. After
lineage commitment, cells are completely dependent on these growth
factors for continued proliferation and viability. More recently,
TNF-
has also been implicated in growth regulation for macrophage
precursors.
The
blood monocytes are young cells that already possess
migratory, chemotactic, pinocytic and phagocytic activities, as
well as receptors for IgG Fc-domains (Fc
R)
and iC3b complement.
Under migration into tissues, monocytes undergo further
differentiation (at least one day) to become multifunctional
tissue macrophages. Monocytes are generally, therefore, considered
to be immature macrophages. However, it can be argued that
monocytes represent the circulating macrophage population and
should be considered fully functional for their location, changing
phenotype in response to factors encountered in specific tissue
after migration.
Macrophages can be divided into normal and inflammatory macrophages. Normal macrophages includes macrophages in connective tissue (histiocytes), liver (Kupffer's cells), lung (alveolar macrophages), lymph nodes (free and fixed macrophages), spleen (free and fixed macrophages), bone marrow (fixed macrophages), serous fluids (pleural and peritoneal macrophages), skin (histiocytes, Langerhans's cell) and in other tissues.
The macrophage population in a particular tissue may be maintained by three mechanisms: influx of monocytes from the circulating blood, local proliferation and biological turnover. Under normal steady-state conditions, the renewal of tissue macrophages occurs through local proliferation of progenitor cells and not via monocyte influx. Originally, it was thought that tissue macrophages were long-living cells. More recently, however, it has been shown that depending on the type of tissue, their viability ranges between 6 and 16 days.
Inflammatory macrophages are present in various exudates. They may be characterized by various specific markers, e.g. peroxidase activity, and since they are derived exclusively from monocytes they share similar properties. The term exudate macrophages designates the developmental stage and not the functional state.
Macrophages are generally a population of ubiquitously distributed mononuclear phagocytes responsible for numerous homeostatic, immunological, and inflammatory processes. Their wide tissue distribution makes these cells well suited to provide an immediate defence against foreign elements prior to leukocyte immigration. Because macrophages participate in both specific immunity via antigen presentation and IL-1 production and nonspecific immunity against bacterial, viral, fungal, and neoplastic pathogens, it is not surprising that macrophages display a range of functional and morphological phenotypes.