Reticular tissue is a special subtype of connective tissue that is indistinguishable during routine histological staining. Its subunits, the reticular fibers, are predominant structures in the human body, but they are mainly scattered and mixed with other types of fibers. They are present in relatively high amounts to form a tissue in extremely specific locations that consist of a high cellular content. This article will describe the characteristics, location, synthesis, and associated clinical points related to reticular tissue and its fibers.
Reticular tissue is a special type of connective tissue that predominates in various locations that have a high cellular content. It has a branched and mesh-like pattern, often called reticulum, due to the arrangement of reticular fibers (reticulin). These fibers are actually type III collagen fibrils. In comparison to the predominant type I collagen, type III fibrils are narrower, do not form thick filaments, and have a higher content of carbohydrates. They consist of collagen molecules, each one being a trimer of three alpha-1 chains. These fibrils display a 68 nanometer (nm) banding pattern. Upon examination by transmission electron microscopy (TEM), the fibrils consist of aggregations of several transverse bands, with a distance of 68 nm between the two adjacent aggregations.
These types of fibers are also present in small amounts in other types of connective tissue. In fact, they are the first to develop in the structure of every tissue that contains them, highlighting their important support role. Reticular fibers support the early synthesized extracellular matrix during wound healing, scar tissue formation, and general development. As maturity or repair continues, the majority of them are replaced by the stronger type I collagen.
For visualization purposes, reticular fibers require special staining procedures because they stain poorly with hematoxylin-eosin (H&E). Some of these include:
- Periodic acid-Schiff (PAS) reaction, which takes advantage of the high polysaccharide content of reticular fibers.
- Gomori and Wilder silver nitrate staining procedures, which make the fibers appear black (argyrophilic).
Some highly cellular locations containing reticular tissue include the endocrine glands, liver, bone marrow, and lymphoid organs. If you think about the structure of those tissues and organs, they all consist of heavily branching septa and internal channels. Reticular tissue also resembles a branched mesh that coincides with the path taken by those septa and channels, almost fitting them “like a glove”. Therefore, the role of the reticular scaffold is to support the cells and the small channels which travel through the respective tissues and organs. For example, in the liver, reticular tissue supports the hepatocytes and the sinusoids.
Reticular fibers are also scattered throughout various locations within the human body, but they do not form reticular tissue. These include:
- Loose connective tissue, where it intersects the epithelium
- Around adipocytes, nerves, small blood vessels, and muscle cells
- Embryonic tissue
- Hematopoietic tissues
- Lymphatic tissues (except the thymus)
In almost all instances, reticular fibers and tissue are produced by fibroblasts. The exception are lymphoid organs and structures, in which reticular cells are responsible for the synthesis. They are a special type of fibroblasts with a variety of additional functions. In lymph nodes, they are located in the cortical and medullary zones. Their morphology is highly variable, ranging from elongated to fusiform or stellate. Reticular cells contain an internal tubular system that communicates with the extracellular matrix via orifices. The cells are connected to each other, resulting in their internal tubes forming a long channel running through all of them via which synthesized molecules and type III collagen monomers are secreted.
The entire process of reticular fiber synthesis is compartmentalized: procollagen (precursor) is synthesized intracellularly within organelles, the collagen monomers (subunit) at the level of the plasma membrane, while the assembly into reticular fibers takes place in the extracellular matrix. Briefly, the process consists of the following steps:
Procollagen synthesis - Pro-alpha chains (pre-procollagen molecules) are produced in the rough endoplasmic reticulum (rER). They are then subjected to several post translational modifications inside the cisternae of the rER. These include:
- Hydroxylation of lysine and proline residues under the influence of vitamin C
- Glycosylation of the two terminal amino acid groups
- Coiling of three alpha chains and combining into a triple helix
- Hydrogen and disulfide bonds are formed to stabilize and shape the molecule, resulting in procollagen
- Procollagen molecules are transported to the Golgi apparatus and then to the cell surface.
- Collagen molecule synthesis - Procollagen molecules are converted to collagen ones via the action of the enzyme procollagen peptidase, which is associated with the plasma membrane.
- Collagen fibrils synthesis - The fibroblasts or reticular cells orientate their secretory vesicles towards special plasma membrane invaginations called coves. The molecules are released and joined longitudinally and cross-linked transversely, ultimately forming polymerized fibrils and then reticular fibers.
Ehlers-Danlos Syndrome type IV
Ehlers-Danlos syndrome (EDS) type IV, or the vascular type, is a condition that arises from abnormalities in type III collagen. The main cause is genetic, involving three types of autosomal dominant mutations in the gene encoding type III collagen. These mutations result in disturbances in the synthesis of reticular fibers. Specifically, three aspects can be affected: the production of the pro-alpha1 chains, the secretion of the procollagens and/or the synthesis of collagen molecules.
It is quite a rare disease that is associated with high morbidity and mortality rates due to its severe manifestations. These include:
- Easy bruising
- Visible veins
- Pale and thin skin
- Certain characteristic facial features
- Ruptures of blood vessels and internal organs