Mechanism of monocyte migration

Chemokine-driven migration of monocytes and DC progenitors.

In mice, two populations of circulating monocytes exist: resident monocytes (Mac1⁺Gr1^-F4/80⁺CX₃CR1^hi) and inflammatory monocytes (Mac1⁺Gr1⁺F4/80⁺CX₃CR1^midCCR2⁺). In the absence of an inflammatory stimulus, CX₃C-chemokine ligand 1 (CX₃CL1; also known as fractalkine) and CC-chemokine ligand 3 (CCL3; also known as macrophage inflammatory protein 1, Mip1) preferentially induce the recruitment of resident monocytes into tissues, whereas CCL2 (also known as monocyte chemotactic protein 1, Mcp1) recruits inflammatory monocytes to inflamed tissue. By contrast, dendritic cell (DC) precursors can be recruited directly from the blood to the lymphoid organs, through signalling induced by CC-chemokine receptor 5 (CCR5)–CCL3 interactions. Direct recruitment of inflammatory monocytes to lymph nodes can occur through high endothelial venules (HEVs) and is mediated by CXC-chemokine ligand 9 (CXCL9; also known as monokine induced by interferon-, Mig). After migration to the peripheral tissue, activated inflammatory monocytes can differentiate into DCs and gain access to the draining lymph nodes through the lymphatics. Inflammation leads to upregulation of CCL21 expression by the lymphatics and upregulation of CCR7 by antigen-presenting cells. Activated resident DCs or newly recruited granulocytes can produce factors that inhibit these differentiation pathways and routes of migration. CX₃CR1, CX₃C-chemokine receptor 1.