Monocytes make up 10 percent of the white blood cells in the blood and play critical roles in development, homeostasis and immunity. As professional phagocytes, they recognize and engulf pathogens, infected cells, lipids and cellular debris. They also promote immune system responses by acquiring and presenting antigens, migrating to sites of inflammation and producing cytokines. Finally, myeloid cells act as a reservoir to replenish a subset of macrophages and dendritic cells.
Monocytes can be divided into two main subpopulations based on their phenotype and function: classical monocytes (CD14++CD16-) and non-classical monocytes (CD14+CD16++). In addition, an intermediate monocyte subpopulation (CD14++CD16+) has been identified, further highlighting the heterogeneity of this cell population.
Classical monocytes, which contain approximately 80 to 90 percent of circulating blood monocytes, have higher levels of phagocytic and antimicrobial activity, associated with sensory and immune responses and cell migration. These monocytes exhibit higher peroxidase activity and have been found to be more efficient at generating reactive oxygen species (ROS). They also produced higher levels of chemokine receptors, suggesting possible migration to sites of injury and inflammation. This type of cells differentiates into macrophages and dendritic cells.
Non-classical monocytes were associated with reduced phagocytosis, ROS and production of proinflammatory cytokines compared with classical monocytes. Instead of performing more traditional monocyte functions, they are known to patrol blood vessel walls, promote wound healing and respond to viral infections. This subpopulation does not proliferate to the same extent as conventional monocytes, but can circulate in the blood for longer periods of time.
Intermediate monocytes, which express CD14 and CD16 (CD14++CD16+) in humans and intermediate levels of Ly6C in mice. Like classical monocytes, this subpopulation displays inflammatory properties. However, like non-classical monocytes, they have low peroxidase activity and secrete TNF and IL-1B. It is suspected that they play an important role in antigen presentation and rapid pathogen defence, as they have been found to be elevated in patients with systemic infections such as HIV.
Identifying and tracking monocytes in complex biological systems requires the use of specific markers. Several markers have been identified and widely used to discriminate monocytes from other immune cell populations. CD14 and CD16 are the most commonly used markers to classify monocytes into subsets. CD14 is a co-receptor for lipopolysaccharides (LPS) and is highly expressed in classical monocytes. CD16, also known as FcγRIII, is an Fc receptor involved in antibody-dependent cell-mediated cytotoxicity and is more abundant in non-classical monocytes. The following shows other key monocyte markers for humans and mice.
Species | Markers |
---|---|
Human | CD2, CD11b, CD31, CD56, CD62L, CD115, CD192, CX3CR1, CXCR3, CXCR4, CCR5, CD86, CD11c, HLA-DR, etc. |
Mouse | CCR2, CD11b, CD16/CD32, CD31, CD43, CD44, CD45, CD62L, CD115, CX3CR1, F4/80, Gr1, Ly-6C, VEGF, CD209, etc. |
Monocytes have toll-like receptors on the cell membrane that can interact with pathogen-associated molecular patterns that occur when invading pathogens occur. This action produces a signal that leads to the migration of monocytes from the bone marrow into the peripheral circulation within 12 to 24 hours. For monocytes to enter the diseased area, they first bind to the endothelium and then move across the vessel surface. Finally, monocytes adhere to endothelial cells, penetrate the endothelial basement membrane and migrate to areas of inflammation. Differentiation of monocytes occurs at sites of inflammation and is dependent on growth factors and cytokines produced during the process. Monocytes in areas of inflammation can also act as phagocytes, engulfing microorganisms, foreign material, dead and damaged cells.
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