Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages

Abstract

In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

Proteomic fingerprints distinguish microglia, bone marrow, and spleen macrophage populations

“…Indeed, MP show unique proteomic profiles even when cultured under identical conditions. These results serve to extend prior MP phenotypic heterogeneity studies, including M-CSF dependency (Cecchini et al, 1994;Naito et al, 1996;de Villier et al, 1998).…”

“…Whether this translates into functional (Gordon et al, 1988) and antigenic differences (Taylor et al, 2003;Guillemin and Brew, 2004) is not completely understood. MP heterogeneity may be simply a consequence of cell exposure to the tissue microenvironment including local growth factors (Naito et al, 1996). The latter would include, but not be limited to, macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF and GM-CSF), that affect MP differentiation, proliferation and activation (Kaplan et al, 1992;Cecchini et al, 1994;de Villiers et al, 1994de Villiers et al, , 1998Hamilton, 1997).…”

Differential contributions of haematopoietic stem cells to foetal and adult haematopoiesis: insights from functional analysis of transcriptional regulators

“…Despite a recent resurgence of the debate over the exact topography of HSC emergence in the mammalian embryo (Samokhvalov et al, 2007), the prevalent view on blood formation is that it follows a two-wave model (reviewed in Godin and Cumano, 2002). The first wave of haematopoiesis-mouse embryonic days (E) 7-8.5-produces primitive erythrocytes (both nucleated and enucleated; Kingsley et al, 2004), megakaryocytes (Tober et al, 2007) and macrophages (Naito et al, 1996), that emerge as uni-and bilineage-committed progenitors (Tober et al, 2007); it does not produce HSC as defined by the capacity to reconstitute haematopoiesis in an adult organism (Cumano et al, 2001). In mammals, this inaugural blood production is extra-embryonic and locates to the blood islands in the YS.…”

Distinct Differentiation Potential of Blood Monocyte Subsets in the Lung

“…Accordingly, when cultured in vitro in the presence of the cytokines M-CSF or GM-CSF, monocytes can be driven to differentiate into M⌽ and DC, respectively (3,4). Furthermore, in vivo studies also provide evidence that blood monocytes can act as precursors of M⌽ (1,5,6). More recent reports have shown that monocytes can under inflammatory conditions differentiate in vivo into conventional CD11c high DC (cDC) (7,8) and Langerhans cells (9).…”