NON-KERATINOCYTES OF THE ORAL MUCOSA
Author: Sanketh DS, MDS
The term oral mucosa or oral mucous membrane is used to describe the moist lining of the oral cavity. Oral mucosa is essentially made of an epithelium and an underlying connective tissue. The epithelial cells are called keratinocytes due to the presence of intermediate filaments called cytokeratins which are bundled into tonofilaments. Keratinocytes are firmly attached to each other with the help of intercellular-bridges called desmosomes. The epithelial cells or keratinocytes in the lower layers divide and produce new cells, which in turn undergo maturation as they keep moving up layers and replace cells that are eventually shed.
Non-keratinocytes constitute a small group of cells in the epithelium that are unlike keratinocytes. They are very few in number, do not possess cytokeratin filaments (hence do not keratinize), are not attached to the cells of the epithelium with desmosomes and do not undergo maturation like the keratinocytes. Under the microscope in an H and E stained section, these cells appear to have a halo around the nucleus. This is because the cytoplasm around the nucleus shrinks during the histologic processing of the tissue. Hence they are also called “clear cells”. Non-keratinocytes comprise a variety of cells that include a) melanocytes, b) Langerhans cells, c) Merkel cells and d) inflammatory cells (mostly lymphocytes).
TYPES OF NON-KERATINOCYTES
Melanocytes are derived from neural crest cells and are dendritic cells situated in the basal layer of the oral epithelium. Melanocytes and keratinocytes associate with each other by forming, what is called an epidermal melanin unit. It is estimated that, a unit may have one melanocyte associated with at least 36 keratinocytes, with its dendritic processes passing through the layers of the epithelium. Melanocytes attach to the adjacent keratinocytes through tight and gap junctions.
Melanocytes are specialized pigment cells that produce melanin which contributes to the colour of the oral mucosa in the individual. Melanin pigments are produced inside of organelles called melanosomes. These melanin pigment containing melanosomes are transported into keratinocytes via the melanocyte’s dendritic processes. Dark skinned individuals more often show physiologic pigmentation of the oral mucosa and is most commonly seen in the gingiva, buccal mucosa, hard palate and tongue.
The difference in pigmentation seen in dark and light skinned individuals is not due to the difference in the number of melanocytes. The number is more or less the same; the difference lies in the activity of the melanocyte i.e in the amount of melanin produced in the individual.
In individuals with heavy pigmentation, melanin containing cells can be seen in the connective tissue. These are macrophages that have ingested melanosomes and are called melanophages. Apart from imparting colour, melanin is also known to protect against inflammatory free radicals and have anti-bacterial effects.
Langerhans cells are dendritic cells called antigen presenting cells (APCs) located above the basal layer of the epithelium. These cells are derived from hematopoietic stem cells in the bone marrow. Langerhans cells have an immunologic function. Unlike melanocytes they can move in and out of the epithelium. Their main function is to ingest bacteria or other foreign antigens present in the epithelium, process and break them into peptides and present these peptides to the nearby T-lymphocytes. They could either present them to the T-lymphocytes in the connective tissue or migrate to nearby regional lymph nodes and present them. Langerhans cells are characterized by the presence of rod shaped granules called Birbeck granules that could be visualized ultrastructurally.
Merkel cells are non-keratinocytes located in the basal layer of the oral epithelium. Unlike melanocytes and Langerhans cells, Merkel cells are non-dendritic and known to occasionally possess desmosomes and tonofilaments. Though they were thought to be derived from neural crest cells, recent experiments show they may be of epithelial origin. They are more often found in the masticatory mucosa and are thought to have a sensory function and respond to touch. Merkel cells have been found in increased numbers in mucosa that have been chronically insulted or damaged. It is hence proposed to also have a reparative or a regenerative function.
Merkel cells are usually present in the basal layer, in association with an axon terminal in the connective tissue. Ultrastructurally, these cells have numerous membrane bound vesicles situated in between the nucleus and the axon terminal. The vesicles could release transmitter substances that could trigger the axon terminal generating an impulse.
The oral epithelium may occasionally show few inflammatory cells in various layers. They are mostly lymphocytes, though neutrophils and mast cells may also be present. These cells migrate from the connective tissue and infiltrate the epithelium. Lymphocytes in the epithelium may be associated with Langerhans cells presenting antigens to them. Inflammatory cells have an immunologic function and participate in innate and adaptive immune responses.
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