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Histology, Monocytes
Introduction
Monocytes are white blood cells that derive from the bone marrow. A monocyte is part of the innate immune response and functions to regulate cellular homeostasis, especially in the setting of infection and inflammation.[1] They account for approximately 5% of circulating nucleated cells in normal adult blood.[2] The half-life of circulating monocytes is approximately one to three days.[3] Monocytopenia, a decrease in circulating monocytes, is a common finding in myelodysplastic syndromes.[4] While monocytosis, an increase in circulating monocytes, is a common finding in the peripheral blood, especially in association with infection, trauma, medications, autoimmune disease, and some malignancies.[1] When monocytosis is persistent and unexplained, the diagnosis of chronic myelomonocytic leukemia merits investigation.[5]
Issues of Concern
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Issues of Concern
When there is a suspected myeloid neoplasm with monocytic differentiation, it is challenging and essential to accurately classify monocytes as mature or immature. There is no definitive test to identify immature monocytes. Flow cytometry identifies molecules on the surface of such cells, known as cluster of differentiation (CD) markers. Such markers can provide information to help in estimating the approximate populations of mature and immature monocytes.[6] Along with flow cytometry, the cell’s morphology requires assessment due to the atypical expression of CD markers during neoplastic growth.[5] In chronic myelomonocytic leukemia, there is persistent peripheral blood monocytosis with approximately double the amount of normally circulating monocytes.[5] The bone marrow must have less than 20% blasts (immature cells) present for the clinician to render a diagnosis of chronic myelomonocytic leukemia.[7]
Structure
Monocytes are the largest white blood cell, measuring between 12 to 20 µm in diameter, approximately twice the size of red blood cells.[2] Monocytes are typically easy to identify in the peripheral blood by their relatively large size and convoluted bilobed nuclei, often described as kidney-shaped.[8]
Function
Monocytes are a crucial component of the innate immune system.[9] A monocyte is a type of white blood cell that differentiates into populations of macrophages and dendritic cells to regulate cellular homeostasis, especially in the setting of infection and inflammation.[1] Monocytes have two distinct roles; they regularly patrol the body for microbial cells and orchestrate an immune response in times of infection and inflammation.[1] Monocytes have toll-like receptors on their surfaces that interact with PAMPS (pathogen-associated molecular patterns) found on invading microbial cells.[10] In response to such stimuli, monocytes migrate from the bone marrow into the blood circulation and infiltrate tissues within 12 to 24 hours.[11]
To infiltrate the affected sites, the monocytes must first secure themselves to the endothelium and then loosely roll along the vascular surface. The monocyte then firmly adheres to the endothelium and finally passes through the endothelial cells through a process known as diapedesis. Monocytes are then able to penetrate the endothelial basement membrane and migrate to the area of inflammation.[12] This process occurs through the interaction of molecules on both the monocyte and the endothelial cell surfaces.[13] Growth factors and cytokines determine the monocyte subtype.[14] Monocytes function as phagocytes and antigen-presenting cells in the peripheral blood to ingest and remove microorganisms, foreign material, and dead or damaged cells.[1] Antigen-presenting cells include macrophages, dendritic cells, B lymphocytes, and activated endothelial cells.[15]
Macrophages can further differentiate into specialized macrophages based on their location.[16] These include histiocytes in the connective tissue, microglia cells in the brain, osteoclast in the bone, mesangial cells in the kidney, and alveolar macrophages in the lungs.[17] Monocytes can produce cytokines that recruit additional cells and proteins to the affected area mounting a substantial immune response.[1] The types of cytokines released will vary depending on the function.[18] To restore homeostasis, monocytes can contribute to remodeling and healing via anti-inflammatory cytokines.[18]
Tissue Preparation
The histological characterizing of monocytes occurs in three main steps. These steps include obtaining and preparing a sample of whole blood, flow cytometry, and monocyte gating. The process of preparing the whole blood is a multistep chemical procedure that involves lysing the cells, marking the cells, and ultimately obtaining a concentrated sample for use in the study. Flow cytometry of the sample then allows for the characterizing of the monocytes depending on the markers they process. Monocyte gating is a visual means by which to organize the collected data to show the percentage of each monocyte subset.[19]
Histochemistry and Cytochemistry
The cluster of differentiation (CD) markers are specific molecules found on the surface of a cell that differentiates cells from one another, as well as from surrounding tissue. The CD markers are specific to the subtype of monocyte and the type of response mounted by the immune system.[6] Common CD markers include CD4, CD11b, CD14, CD16, and CD33.[20]
Microscopy, Light
The single bi-lobed nucleus has mature chromatin, and the cytoplasm is moderate to abundant and frequently shows irregular basophilic edges. Upon staining with non-specific esterases, the nucleus is pale violet, while the abundant cytoplasm stains pale grey to blue with numerous reddish-blue cytoplasmic granules.[2]
Microscopy, Electron
On electron microscopy, monocytes appear to have a single nucleus and abundant cytoplasm with scattered granules as well as organelles. Such organelles include numerous mitochondria, a Golgi apparatus, microvesicles, microtubules, and microfilaments.[21]
Pathophysiology
The role of monocytes is versatile and related to various types of disorders and infectious processes, and inflammation. Monocytosis and monocytopenia have been identifying factors in multiple hematologic disorders, such as leukemias and myelodysplastic syndromes.[22] Monocytosis is present in numerous inflammatory and immune disorders, such as connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and sarcoidosis.[23][24][25] Monocytes play a crucial role in the immune response to acute infectious and inflammatory processes, such as mycobacterial infections and varicella-zoster virus.[26][27] Monocytosis also occurs in myocardial infarction and is often related to the serum creatinine kinase and extent of infarction.[28] Monocytes can remove the debris and help with remodeling following myocardial infarctions.[29]
Clinical Significance
Monocytes are a critical component of the innate immune system. They are the source of many other vital elements of the immune system, such as macrophages and dendritic cells. Monocytes play a role in both the inflammatory and anti-inflammatory processes that take place during an immune response. Monocytes, and their abundance or lack thereof, can provide significant identifying clues for the diagnosis of several hematologic disorders and inflammatory and immune disorders.
Media
(Click Image to Enlarge)
Monocyte, Neutrophil, and Basophil. This image shows a peripheral blood smear with red blood cells in the background and 3 leukocytes, a monocyte, a neutrophil, and a basophil.
Contributed by D Lynch, MD
References
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