Monocytes are amoeboid in appearance, and have nongranulated cytoplasm. Thus they are classified as agranulocytes. Containing unilobar nuclei, these cells are one of the types of mononuclear leukocytes which shelter azurophil granules. The archetypal geometry of the monocyte nucleus is ellipsoidal; metaphorically bean-shaped or kidney-shaped, although the most significant distinction is that the nuclear envelope should not be hyperbolically furcated into lobes. Contrast to this classification occurs in polymorphonuclear leukocytes. Monocytes compose 2% to 10% of all leukocytes in the human body and serve multiple roles in immune function. Such roles include: replenishing resident macrophages under normal conditions; migration within approximately 8-12 hours in response to inflammation signals from sites of infection in the tissues; and differentiation into macrophages or dendritic cells to effect an immune response. In an adult human, half of the monocytes are stored in the spleen. These change into macrophages after entering into appropriate tissue spaces, and can transform into foam cells in the endothelium.
There are at least three types of monocytes in human blood:
The classical monocyte is characterized by high level expression of the CD14 cell surface receptor (CD14++ CD16- monocyte)
The non-classical monocyte shows low level expression of CD14 and additional co-expression of the CD16 receptor (CD14+CD16++ monocyte).
The intermediate monocyte with high level expression of CD14 and low level expression of CD16 (CD14++CD16+ monocytes).
While in humans the level of CD14 expression can be used to differentiate non-classical and intermediate monocytes, the slan (6-Sulfo LacNAc) cell surface marker was shown to give an unequivocal separation of the two cell types.
Ghattas et al. state that the "intermediate" monocyte population is likely to be a unique subpopulation of monocytes, as opposed to a developmental step, due to their comparatively high expression of surface receptors involved in reparative processes (including vascular endothelial growth factor receptors type 1 and 2, CXCR4, and Tie-2) as well as evidence that the "intermediate" subset is specifically enriched in the bone marrow. After stimulation with microbial products the CD14+CD16++ monocytes produce high amounts of pro-inflammatory cytokines like tumor necrosis factor and interleukin-12.
Said et al. showed that activated monocytes express high levels of PD-1 which might explain the higher expression of PD-1 in CD14+CD16++ monocytes as compared to CD14++CD16- monocytes. Triggering monocytes-expressed PD-1 by its ligand PD-L1 induces IL-10 production which activates CD4Th2 cells and inhibits CD4Th1 cell function.
In humans a monocyte crawling behavior, similar to the patrolling in mice, has been demonstrated both for the classical and the non-classical monocytes.[clarification needed]
In mice, monocytes can be divided in two subpopulations. Inflammatory monocytes (CX3CR1low, CCR2pos, Ly6Chigh, PD-L1neg), which are equivalent to human classical CD14++ CD16- monocytes and resident monocytes (CX3CR1high, CCR2neg, Ly6Clow, PD-L1pos), which are equivalent to human non-classical CD14+ CD16+ monocytes. Resident monocytes have the ability to patrol along the endothelium wall in the steady state and under inflammatory conditions.
Macrophages are responsible for protecting tissues from foreign substances, but are also suspected to be important in the formation of important organs like the heart and brain. They are cells that possess a large smooth nucleus, a large area of cytoplasm, and many internal vesicles for processing foreign material.
Monocytes and their macrophage and dendritic cell progeny serve three main functions in the immune system. These are phagocytosis, antigen presentation, and cytokine production. Phagocytosis is the process of uptake of microbes and particles followed by digestion and destruction of this material. Monocytes can perform phagocytosis using intermediary (opsonising) proteins such as antibodies or complement that coat the pathogen, as well as by binding to the microbe directly via pattern-recognition receptors that recognize pathogens. Monocytes are also capable of killing infected host cells via antibody-dependent cell-mediated cytotoxicity. Vacuolization may be present in a cell that has recently phagocytized foreign matter.
Microbial fragments that remain after such digestion can serve as antigens. The fragments can be incorporated into MHC molecules and then trafficked to the cell surface of monocytes (and macrophages and dendritic cells). This process is called antigen presentation and it leads to activation of T lymphocytes, which then mount a specific immune response against the antigen.
Other microbial products can directly activate monocytes and this leads to production of pro-inflammatory and, with some delay, of anti-inflammatory cytokines. Typical cytokines produced by monocytes are TNF, IL-1, and IL-12.
Monocytic cells may contribute to the severity and disease progression in Covid-19 patients.
A scanning electron microscope (SEM) image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.
A monocyte count is part of a complete blood count and is expressed either as a percentage of monocytes among all white blood cells or as absolute numbers. Both may be useful but these cells became valid diagnostic tools only when monocyte subsets are determined.
Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.
Examples of processes that can increase a monocyte count include:
A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)
In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.
CMML patients are characterized by a persistent monocyte count of > 1000/ microL of blood. Analysis of monocyte subsets has demonstrated predominance of classical monocytes and absence of CD14lowCD16+ monocytes.
The absence of non-classical monocytes can assist in diagnosis of the disease and the use of slan as a marker can improve specificity.
Monocytopenia is a form of leukopenia associated with a deficiency of monocytes.
A very low count of these cells is found after therapy with immuno-suppressive glucocorticoids.