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A histiocyte is a cell that is part of the human immune system; a tissue macrophage cell^[1][2][3] ("histo-" = "tissue", and "-cyte" = "cell".) Some sources also consider Langerhans cell derivatives to be histocytes.^[4]

All categories of histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and stop in various organs where they undergo differentiation into histiocytes which are part of the mononuclear phagocytic system (MPS).

Histiocytes have common histological and immunophenotypical characteristics (demonstrated by immunostains). Their cytoplasm is eosinophilic and contains variable amounts of lysosomes. They bear membrane receptors for opsonins, such as IgG and the fragment C3b of complement. They express LCAs (leucocyte common antigens) CD45, CD14, CD33 and CD4 (also expressed by T Helper Cells). These histiocytes are part of the immune system by way of two distinct functions: phagocytosis and antigen presentation. Phagocytosis is the main process of macrophages and antigen presentation the main property of dendritic cells (so called because of their star-like cytoplasmic processes). Macrophages and dendritic cells are derived from common bone marrow precursor cells that have undergone different differentiation (as histiocytes) under the influence of various environmental (tissue location) and growth factors such as GM-CSF, TNF and IL-4. The various categories of histocytes are distinguishable by their morphology, phenotype and size.

Macrophages are highly variable in size and morphology, their cytoplasm contains numerous acid phosphatase laden lysosomes - in relation to their specialised phagocytic function. They express CD68.

Dendritic cells have an indented (bean shaped) nucleus and cytoplasm with thin processes (dendritic). Their main activity is antigen presentation, they express Factor XIIIa, CD1c and Class II HLA antigens.

A subset of cells differentiates into Langerhans cells; this maturation occurs in the squamous epithelium, lymph nodes, spleen, and bronchiolar epithelium. Langerhans cells are antigen presenting cells but have undergone further differentiation. Skin Langerhans cells express CD1a as do cortical thymocytes (cells of the cortex of the thymus gland). They also express S-100, and their nucleus contains tennis-racket like ultra-structural inclusions called Birbeck granules.

Histiocytoses describe neoplasias where the proliferative cell is the histiocyte.