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Monocyte

Monocyte

Overview
Monocytes are a type of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

 and are part of the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...

 of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s including all mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s (including human
Human
Humans are the only living species in the Homo genus...

s), bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...

s, reptile
Reptile
Reptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...

s, and fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

. Monocytes play multiple roles in immune function. Such roles include: (1) replenish resident macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s and dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s under normal states, and (2) in response to inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 signals, monocytes can move quickly (approx. 8-12 hours) to sites of infection in the tissues and divide/differentiate into macrophages and dendritic cells to elicit an immune response. Half of them are stored in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

. Monocytes are usually identified in stained smears by their large kidney shaped or notched nucleus.
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Encyclopedia
Monocytes are a type of white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

 and are part of the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...

 of vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s including all mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s (including human
Human
Humans are the only living species in the Homo genus...

s), bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...

s, reptile
Reptile
Reptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...

s, and fish
Fish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...

. Monocytes play multiple roles in immune function. Such roles include: (1) replenish resident macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s and dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s under normal states, and (2) in response to inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 signals, monocytes can move quickly (approx. 8-12 hours) to sites of infection in the tissues and divide/differentiate into macrophages and dendritic cells to elicit an immune response. Half of them are stored in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

. Monocytes are usually identified in stained smears by their large kidney shaped or notched nucleus.

Physiology



Monocytes are produced by the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

 from haematopoietic stem cell precursors called monoblast
Monoblast
Monoblasts are normally found in bone marrow and do not appear in the normal peripheral blood. They mature into monocytes which, in turn, develop into macrophages.-Structure:...

s. Monocytes circulate in the bloodstream for about one to three days and then typically move into tissues throughout the body. They constitute between three to eight percent of the leukocytes in the blood. Half of them are stored as a reserve in the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

 in clusters in the red pulp's Cords of Billroth
Cords of Billroth
The Cords of Billroth are found in the red pulp of the spleen between the sinusoids, consisting of fibrils and connective tissue cells with a large population of monocytes and macrophages...

. In the tissues monocytes mature into different types of macrophages at different anatomical locations. Monocyte is the largest corpuscle in the blood.

Monocytes which migrate from the bloodstream to other tissues will then differentiate into tissue resident macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s or dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s. 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, brain. They are cells that possess a large smooth nucleus, a large area of cytoplasm and many internal vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...

 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
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 or complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

 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, termed antibody-mediated cellular cytotoxicity. Vacuolization
Vacuolization
Vacuolization is the formation of vacuoles within or adjacent to cells, and, in dermatopathology, often refers to the basal cell-basement membrane zone area....

 may be present in a cell that has recently phagocytized foreign matter.

Microbial fragments that remain after such digestion can serve as antigen. The fragments can be incorporated into MHC molecules and then traffic to the cell surface of monocytes (and macrophages and dendritic cells). This process is called antigen presentation
Antigen presentation
Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....

 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 cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s. Typical cytokines produced by monocytes are TNF tumor necrosis factor
Tumor necrosis factor
Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction...

, IL-1 interleukin-1 and IL-12 interleukin-12.

Monocyte subpopulations


There are at least three types of monocytes in human blood :

a) the classical monocyte is characterized by high level expression of the CD14
CD14
Cluster of differentiation 14 also known as CD14 is a human gene.The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms. Either it is anchored into the membrane by a glycosylphosphatidylinositol tail or it appears in a soluble form...

 cell surface receptor (CD14++ CD16- monocyte)

b) the non-classical monocyte shows low level expression of CD14 and with additional co-expression of the CD16
CD16
CD16 is a low affinity Fc receptor.It is a cluster of differentiation found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes and macrophages...

 receptor (CD14+CD16++ monocyte).

c) the intermediate monocyte with high level expression of CD14 and low level expression of CD16 (CD14++CD16+ monocytes).

There appears to be a developmental relationship in that the classical monocytes develop into the intermediate monocytes to then become the non-classical monocytes CD14+CD16+ monocytes. Hence the non-classical monocytes may represent a more mature version. After stimulation with microbial products the CD14+CD16++ monocytes produce high amounts of pro-inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

s like tumor necrosis factor
Tumor necrosis factor
Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction...

 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 inhibits CD4 T-cell function.

Diagnostic use



A monocyte count is part of a complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

 and is expressed either as a ratio of monocytes to the total number of white blood cells counted, or by absolute numbers. Both may be useful in determining or refuting a possible diagnosis.

Monocytosis


Monocytosis
Monocytosis
Monocytosis is an increase in the number of monocytes circulating in the blood. Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system....

 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:
  • chronic inflammation
  • stress
    Stress (medicine)
    Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

     response
  • hyperadrenocorticism
  • immune-mediated disease
    Immune-mediated disease
    Immune-mediated diseases are conditions which result from abnormal activity of the body's immune system. The immune system may over-react or start attacking the body . Autoimmune diseases are a subset of immune-mediated diseases....

  • pyogranulomatous disease
  • necrosis
    Necrosis
    Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

  • red cell
    Red blood cell
    Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

     regeneration
  • Viral Fever
  • sarcoidosis
    Sarcoidosis
    Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...



A high count of CD14+CD16+ monocytes is found in severe infection (sepsis) and a very low count of these cells is found after therapy with immuno-suppressive glucocorticoids

Monocytopenia


Monocytopenia
Monocytopenia
Monocytopenia is a form of leukopenia associated with a deficiency of monocytes. The causes of monocytopenia include: acute infections, stress, treatment with glucocorticoids, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs and genetic syndromes.It has...

 is a form of leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....

 associated with a deficiency of monocytes.

Dendritic cells


Monocytes can be used to generate dendritic cells in vitro by adding cytokines like Granulocyte Monocyte Colony Stimulating Factor (GMCSF) and IL-4.

Blood content



See also

  • Agranulocyte
    Agranulocyte
    Agranulocytes are a category of white blood cells characterised by the absence of granules in their cytoplasm.There are two types of agranulocytes:* Lymphocytes* Monocytes....

  • Complete blood count
    Complete blood count
    A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...

  • Hematopoiesis
  • Neutrophil granulocyte
    Neutrophil granulocyte
    Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...

  • Phagocyte
    Phagocyte
    Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...

  • White blood cell
    White blood cell
    White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...


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