Figure 1 Monocyte and macrophage ontogeny

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Figure 1 Monocyte and macrophage ontogeny Figure 1 | Monocyte and macrophage ontogeny. Monocytes derive from haematopoietic precursors in bone marrow or spleen, and give rise to classical — lymphocyte antigen 6C (LY6C)high in mice and CD14highCD16low in humans — and nonclassical — LY6Clow in mice and CD14lowCD16high in humans — subsets. Production and emigration of monocyte subsets depend on defined signals and chemokine receptors, such as C-C motif chemokine 2 (CCL2)36,80, C-C chemokine receptor type 2 (CCR2)15,36,38,73,248,249, and C-X-C chemokine receptor type 4 (CXCR4)59 for LY6Chigh monocytes, and miR-146 (Ref. 31), nuclear receptor subfamily 4 group A member 1 (NR4A1)53, transcription factor RelB31, and sphingosine 1-phosphate receptor 5 (S1PR5)250 for LY6Clow monocytes. Some monocytes remain attached to the endothelium and patrol the blood vessel lumen; other LY6Clow monocytes can derive from LY6Chigh monocytes. Inflammatory cues induce monocyte extravasation (particularly of LY6Chigh monocytes) and polarization into macrophages. Monocyte-derived macrophages mix with tissue-resident macrophages derived from yolk sac and fetal liver precursors. The macrophage pool receives tissue specific signals to define phenotypes and effector functions and, along with other cues such as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), define the spectrum of tissue macrophages found in vivo. Dotted lines represent hypothesized or unknown pathways. AGTR1A, type 1A angiotensin II receptor; Ang II, angiotensin II; cMoP, common monocyte progenitor; CMP, common myeloid progenitor; CX3CL1, CX3C-chemokine ligand 1; CX3CR1, CX3C-chemokine receptor 1; GMP, granulocyte–macrophage progenitor; HSC, haematopoietic stem cell, ICAM, intercellular adhesion molecule; int, intermediate; JAM, junctional adhesion molecule; LFA1, lymphocyte function-associated antigen 1; MDP, macrophage and dendritic cell precursor; PECAM1, platelet endothelial cell adhesion molecule; PSGL1, P-selectin glycoprotein ligand 1; VCAM1, vascular cell adhesion protein 1; VLA4, very late antigen 4. Mohammed Shamim Rahman et al. (2017) Effects of dyslipidaemia on monocyte production and function in cardiovascular disease Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.34