Fibrocyte: Structure, Function & Diseases

Fibrocytes are part of the connective tissue. They are normally in a resting state and have irregular projections that join with the projections of other fibrocytes to give connective tissue three-dimensional strength. When needed, such as after mechanical injury, fibrocytes can “awaken” from their dormancy and revert to fibroblasts by dividing to synthesize components of the extracellular matrix in the intercellular space.

What is a fibrocyte?

Fibrocytes are nonmotile cells of connective tissue and thus part of the extracellular matrix. Their main feature is irregular projections that can connect with the projections of other fibrocytes in the form of so-called tight and gap junctions, giving connective tissue a three-dimensional strength structure. Tight junctions are characterized by narrow bands of membrane proteins that mutually surround the cells, creating a very close contact between the membranes of adjacent cells that also acts as a diffusion barrier. In contrast, in gap junctions, there is no direct membrane contact between two cells. The membranes are kept at a distance of about 2 to 4 nanometers, but they are connected to each other by connexons made of proteins, which also allow some exchange of substances, including messenger substances. Unlike the fibroblasts from which they are derived, fibrocytes are biologically almost inactive. This means that they cannot synthesize elastic fibers or other components of connective tissue. In the case of injuries that require the body’s own repair mechanisms, fibrocytes can be “brought back to life,” dividing and giving rise to two fibroblasts each. The fibroblasts are capable of producing necessary components of scar tissue.

Anatomy and structure

Fibrocytes are immobile, or stationary, cells of connective tissue with an elongated oval nucleus and irregular projections of cytoplasm. They reach a size of about 50 µm. The cells arise from fibroblasts, which are the main component of connective tissue and, unlike fibrocytes, exhibit biological activities. They continuously produce and synthesize components of the extracellular matrix, mainly elastic fibers. The nucleus of fibrocytes contains densely packed chromatin, i.e. densely packed chromosomes. A high number of mitochondria, the power plants of the cell, are incorporated in the cytoplasm. In addition, the cytoplasm contains an above-average amount of rough endoplasmic reticulum and many Golgi structures. The rough endoplasmic reticulum consists of a dynamically changing network of membranes, tubes and cavities that are important for many metabolic processes, including those related to protein synthesis. The Golgi apparatus of a cell is a membrane-enclosed organelle that plays a role primarily in secretion formation.

Function and Tasks

One of the most important tasks of fibrocytes is to provide a certain structural strength of connective tissue by mutual interconnection in a three-dimensional network. In addition, their role is to synthesize precursors of collagen, as well as glycosaminoglycans and proteoglycans. Glycosaminoglycans are an important component of the extracellular matrix. They consist of linear repeats of polysaccharide units and serve to store water in tissues and as biological lubricants. Proteoglycans are large molecules composed of 40 to 60 glycosaminoglycans and a few proteins attached via an oxygen-glycosidic bond. Proteoglycans have a high water-binding capacity and also form the basic substance of tendons, cartilage and sliding surfaces in joints. They also form the main substance of lubricants in joints and are also an important component of the extracellular matrix. In addition, they perform a kind of reserve function. In the event of an injury that requires activation of the body’s repair system, fibrocytes can be reactivated by dividing to give rise to two fibroblasts each, which can cover the full range of activities of a fibroblast. In wound healing, the fibroblasts converted into fibroblasts and the “normal” fibroblasts appear mainly in the granulation and differentiation phases.The task of fibroblasts is to provide the wound with a temporary replacement tissue during the granulation phase and to supply it with building blocks of the extracellular matrix. In the subsequent differentiation phase, it is the responsibility of the fibrocytes and fibroblasts to contract the wound by means of collagen fibers and to synthesize appropriate scar tissue. The process is assisted by macrophages, which break down necrotic tissue and blood clots and provide the amino acids and other basic substances thus released for the formation of new tissue.

Diseases

Diseases and disorders associated with fibrocytes can be caused by deficiencies of certain micronutrients, by underlying diseases, or by one or more genetic defects. For example, scurvy, beriberi, and pellagra are typical diseases caused by deficiencies of certain essential vitamins. Fibrocytes and fibroblasts are disturbed by the deficiency in their synthesis work of producing connective tissue components such as collagens and others, so that connective tissue loses its strength and bleeding, tooth loss and other damage can occur. However, the breakdown of collagen can also be caused by weightlessness, immobilization, and as an undesirable side effect of prolonged treatment with cortisone. The opposite clinical picture exists with fibrosis or sclerosis. Fibrosis is typically manifested by abnormal increased production of interstitial connective tissue by fibrocytes and fibroblasts, resulting in gradual loss of function of the affected organs. Fibrosis can be caused by repetitive mechanical stress or by endogenous factors such as circulatory disorders or chronic inflammation. Well-known examples of loss of organ function due to fibrosis include pulmonary fibrosis and liver cirrhosis. Sclerosis is also symptomatically caused by increased collagen production leading to hardening in the affected tissue such as in arteriosclerosis. Also associated with pathologically increased activity of fibrocytes and fibroblasts are benign tumors of connective tissue, fibromas and lipomas, and malignant tumors such as fibrosarcomas or liposarcomas.