Histiocyte

The term "histiocyte" ( histio= diminutive of "histo" = tissue), i.e. tissue cell, in contrast to lymphocyte and granulocyte, is a completely unspecific term for a 15 to 20 µm large cell of connective tissue, with a large, round-oval, hyperchromatic nucleus and large rounded or cuspate cytoplasm, which gives it an epithelioid or also dendritic aspect. Originally a purely morphological descriptor.

It is now known that histiocytes are derived from the monocytes of the blood. They are cellular components of the mononuclear phagocytotic (MPS), and thus an essential component of the immune system. Their progenitor cells circulate through the body as monocytes, enter various organs hematogenously, where they undergo differentiation into the tissue-resident histiocytes. Their biological function is phagocytosis of cellular debris, bacteria and devitalized cells, with subsequent digestion by hydrolytic enzymes of their lysosomes. Histiocytes have a life span of 2-3 months. They are subsequently eliminated by other tissue macrophages. Histiocytes also retain the ability to divide in connective tissue.

Histiocytes and macrophages are ubiquitously represented. In different organs they have specific, organ-adapted functions (and morphology) and are insofar also designated differently:

• General histiocyte-macrophages: localized in loose connective tissue and very common (30-50% of all cells).
• Microglia (CNS): Origin from the mesoblasts. They take over the role of histiocytes.
• Monocytes (blood): Precursors of histiocytes. They leave the vessels by diapedesis and penetrate the connective tissue.
• Von Kupffer's stellate cells: localized in the wall of liver sinusoids.
• Alveolar macrophages: localized in the pulmonary alveoli. They phagocytize airborne dust and charcoal.
• Peritoneal macrophages
• Osteoclasts: macrophages of the bones.
• Interdigitating and dendritic cells (lymphoid organs): Antigen-presenting cells. They express factor XIIa, CD1c.
• Langerhans cells: Dendritic cells localized in the epidermis. They express CD1a (as do cortical thymocytes), S 100 and contain typical cell organelles (Birbeck granules).
• Cells of the synovial membrane.

Histiocytes have an eosinophilic, lysosome-rich cytoplasm. They possess membrane receptors for opsonins (see opsonization below), for IgG, and the C3b fragment for complement. Histiocytes express LCAs (leucocyte common antigens) as well as CD45, CD14, CD33 and CD4 (see CD classification below) and comprise about 30-50% of the cells in interstitial connective tissue. Macrophages vary widely in size and morphology and are specialized for phagocytic functions.

Tissue macrophages and dendritic cells: These histiocytes are characterized by two distinct functions part of the immune system: phagocytosis and antigen presentation. Phagocytosis is the main process of macrophages and antigen presentation is the main property of dendritic cells, so called because of their star-shaped cytoplasmic projections. Macrophages and dendritic cells are derived from common bone marrow progenitor cells that have undergone different differentiation under the influence of various factors (environmental and growth factors such as GM-CSF, TNF, and IL-4). Macrophages recognize and phagocytose as antigen-presenting cells (APCs), in different ways exogenous materials or pathologically altered endogenous proteins, glycoproteins, lipids. After these (if possible) have been broken down and processed intracellularly, they can be presented to other immune cells together with MHC-I or MHC-II complexes. These immune cells, activated in this way, release a different cytokine pattern (TH1 cytokines, Th2 cytokines) depending on the antigen, recruiting further inflammatory cells from the bloodstream. These in turn now signal back to the macrophages to destroy the previously phagocytosed material. In contrast to dendritic cells (DCs), which also present antigen, activated macrophages have a limited ability to activate naive T cells (i.e., those that have not yet come into contact with an antigen) (see below Antigen presentation

Dendritic cells have an indented (bean-shaped) nucleus and cytoplasm with thin star-shaped projections (dendritic). Their main activity is antigen presentation on their MHC (major histocompatibility complex) molecules; they express factor XIIIa, CD1c and human leukocyte class II antigens (for further subdivision of dendritic cells see there).

Langerhans cells: A subset of dendritic cells differentiates into Langerhans cells; this maturation occurs in squamous epithelium, lymph nodes, spleen and bronchiolar epithelium. Langerhans cells are antigen-presenting cells, but they have undergone further differentiation. Langerhans cells of the skin express CD1a as do cortical thymocytes (cells of the thymic cortex). In addition, they express CD207 (Langerin) and also S-100. Their cytoplasm contains tennis racket-like ultrastructural inclusions called Birbeck granules.

The term histiocyte may also simply refer to a cell of monocytic origin outside the blood system, e.g., in a tissue (as in rheumatoid arthritis as palisade-forming histiocytes surrounding the fibrinoid necrosis of rheumatoid nodules).

Numerous disease names such as histiocytoma (fibrocytic tumor/dermatofibroma), atypical regressive histiocytosis(CD30 positive T-cell lymphoma), cytophagic histiocytic panniculitis (a subcutaneous T-cell lymphoma), and others have been so named because of a morphologic similarity of the proliferating cells to histiocytes of connective tissue. However, they have nothing to do with each other.