Istologia - tessuto connettivo

Histology - Connective tissues I (CT features)

Connective tissues are very important in our body; some play a specific role, others are located in all organs and have a support function. Connective tissue is characterized by irregularly-shaped cells immersed in abundant extracellular matrix, which makes it very different from the epithelial tissue. In the connective tissue, there are many different cells: the more abundant are fibroblasts, but we also find macrophages and mast cells. We also find elastic fibers and collagen fibers.

Primary functions of connective tissue

The primary functions of connective tissue are the following:

• The connection of different tissues to maintain functional integration (in case of epithelial tissue, for example, it provides nourishment).
• Structural support, since it forms a network to sustain other tissues, but there are also specialized connective tissues (such as cartilage and bone tissue).
• It serves as a medium for exchange and regulates metabolites diffusion.
• Protection of organs (in some specific cases, such as the adipose tissue that surrounds kidneys, eyes, and other organs).
• Trophic function, specifically played by the blood, a particular connective tissue.
• Defense function, played again by the blood, but also by other connective tissues that work as a filter to stop bacteria.
• Reparation of damaged tissues, since injured cells can be replaced by connective tissue, such as in the heart after heart ischemia, where connective tissue maintains the integrity of the heart even if it can’t play the proper role.

Composition of connective tissue

Connective tissue is made up of two main groups: cells and extracellular matrix (ECM). Cells can be further divided between resident cells, which live in the connective tissue their whole life, and migrating cells, which are in other tissue but can move in the connective tissue to play a specific role. The extracellular matrix can be distinguished in two main components: fibrillary components (collagen, reticular or elastic fibers) and ground substance (water, electrolytes, glycoproteins, glycosaminoglycans, proteoglycans, and enzymes). Resident cells are responsible for synthesis and degradation of ground substances. The classification of connective tissues is based on the composition of the ECM.

Types of cells in connective tissue

There are different resident cell types: the main ones are fibroblasts, located in most connective tissue; chondroblasts are in the cartilage; osteoblasts are in the bones; blood cells in the blood. They all come from the mesenchyme tissue of the embryo. Migrating cells can be neutrophils, eosinophils, basophils, monocytes (which increase the concentration of macrophages in an attacked area), mastocytes (not always considered a migrating cell), lymphocytes, and plasma cells (which move in the connective tissue to play their defensive function and die there).

Macrophages in connective tissue

Macrophages are resident cells of the connective tissue originated by the differentiation of monocytes. They are specifically involved in the phagocytosis of damaged cells, aged cells, modified cells, ECM components, and during the immune response since they present antigens to other cells of the immune system. They secrete cytokines and enzymes which interact with other immune cells. They are considered “cleaners” of the connective tissue. Macrophages have two different conformations: inactive or activated macrophages. They present two different morphologies and when they are inactive they are “fixed” on the fibers of the ECM, with protrusions that allow this attachment. When they are activated, they detach from the fibers, lose these protrusions, and modify their morphology. Macrophages are specialized in phagocytosis and therefore their cytoplasm has lots of lysosomes and a very well-developed rER, together with abundant Golgi and cytoskeleton to allow the production of the protrusion. Inactive macrophages have a star-like shape, with an eccentric nucleus and some finger-like protrusions that attach them to fibers. When they activate, they detach from the fibers and are able to move in the connective tissue by ameboid movement.

Migrating cells and the ECM

Migrating cells are mainly leukocytes (white blood cells) that leave the bloodstream thanks to some receptor placed in the inner membrane of the blood vessel and reach the surrounding connective tissue to trigger the anti-inflammatory response.

The ECM is formed by many different molecules and substances. There is collagen, which is a protein made by three alpha-chains wrapped one around the other to form a spiral. Fibroblasts synthesize procollagen, which are precursors of collagen with peripheral amino acid chains, preventing procollagen to spontaneously aggregate in the cytoplasm, which are removed from the procollagen in the ECM. Another kind of fibers are the reticular fibers, which form a network, while collagen fibers form a bundle. They’re still formed by fibrils, however. This kind of fibers is typical of reticular connective tissue, which forms the skeleton that holds organs together.

Collagen types and ECM balance

There are eleven types of collagen, but the most important ones are the types I, II, III, and IV. The equilibrium of the collagen content is very important and an increased synthesis or degradation of collagen can lead to many severe pathologies, since collagen is the most abundant protein in our body. Degradation is made by some enzymes, Matrix Metallo-Proteases, present in the ECM. Mutation in collagen fibers leads to organs losing their shape and therefore their function, as well as mutation in bones and cartilages that prevent a child from growing effectively.

Elastic fibers and GAGs

Other important components of the ECM are elastic fibers. They are able to stretch, while collagen fibers are very strong and inelastic. The presence of both kinds of fibers, together with the fibroblasts, with some free space between different components determines a loose connective tissue, while a dense connective tissue has less space and much more fibers. Elastic fibers are present in tissues and organs that have to stretch and change their shape continuously (e.g., blood vessels, lungs, bladder, skin). They are made of a core of elastin with microfibrils of fibrillin. They contain some specific amino acids called desmosine and isodesmosine and are derived from residues of lysine. Elastic fibers can form more than one layer. Elastic fibers are made through elastogenesis. Elastin, the amorphous part, is a big protein that is synthesized as tropoelastin, conjugated with a protein that prevents it to spontaneously aggregate. When tropoelastin is released from the cell, the protein is removed and elastin aggregates. Elastin is then attached to the microfibrils, made up by the polymerization of fibrillin. Elastic fibers are much less abundant than collagen, but still a mutation in them induces severe diseases, such as the Marfan syndrome which may lead to the aortic dissection.

GAGs (GlycosAminoGlycans) are some of the macromolecules dissolved in the ECM, made mainly by water. There are many GAGs in the connective tissue. The most important one is Hyaluronic acid, the only GAG not to be sulfated nor protein-linked. GAGs are formed by chains of sugars and are linked to a protein core. GAGs + protein = proteoglycan. Only the Hyaluronic acid can be found without the protein core. GAGs are negatively charged and can therefore interact with water molecules to help resist external pressures.