Adhesion Molecules

Important classes of extracellular macromolecules are the adhesion molecules. The two major classes of adhesion molecules that provide and maintain intercellular contacts are calcium ion-dependent and calcium ion-independent adhesion molecules. The calcium-dependent adhesion mo­lecules include the cadherins and some selectins, whereas the calcium-independent adhesion molecules include the integrins, the magnesium ion-dependent selectins, and the immunoglobulin superfamily (neural cell adhesion molecules [NCAMs] and intercellular adhesion molecules [ICAMs]).

Cadherins. Cadherins link parts of the internal cytoskele-ton (actin and structures called catenins) with extracellu­lar cadherins of an adjacent cell. This type of linkage is called homophilic, meaning that molecules on one cell bind to other molecules of the same type on adjacent cells (Fig. 4-28). More than 40 different types of cadherins are known, and they are found in such intercellular junctions as the zonula and macula adherens.

Selectins. Selectins bind carbohydrates present on the lig-ands of an adjacent cell in a heterophilic type of interaction (see Fig. 4-28). In heterophilic interactions, the molecules on one cell bind to molecules of a different type on adja­cent cells. Selectins are found on activated endothelial cells of blood vessels, on leukocytes, and on platelets. They, together with integrins and immunoglobulins (Ig), partic­ipate in leukocyte movement through the endothelial lin­ing of blood vessels during inflammation.

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FIGURE 4-28 (A) Homophilic and (B) heterophilic cell adhesions. Examples of a homophilic inter­cellular adhesion between two iden­tical cadherin dimer molecules joined at the N-terminal domain and a heterophilic binding of the lectin domain (A) of an integrin with the carbohydrate portions of a ligand (B). (Courtesy Edward W. Carroll.)

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Integrins. Integrins usually assist in attaching epithe­lial cells to the underlying basement membrane. Unlike other cell adhesion molecules, they are heterodimers consisting of alpha and beta subunits. Extracellularly, they are attached to fibronectin and laminin, the two major components of the basement membrane. Like the cadherins, their intracellular portion is linked to actin (see Fig. 4-28).

One group of integrins is associated with hemidesmo-somes, whereas others are associated with the surface of white blood cells, macrophages, and platelets. Integrins usually have a weak affinity for their ligands unless they are associated with cellular focal contacts and hemidesmo-somes. This allows some movement between cells except where a firm attachment is required to attach epithelial cells to the underlying connective tissue.

Certain integrins play an important role in allowing white blood cells to pass through the vessel wall, a process called transmigration. Persons affected with leukocyte ad­hesion deficiency are unable to synthesize appropriate integrin molecules. As a result, they experience repeated bacterial infections because their white blood cells are not able to transmigrate through vessel walls.

Immunoglobulin Superfamily. NCAMs belong to a super family of immunoglobulins that includes several related types. All types are calcium ion independent but, unlike other adhesion molecules, may participate in homophilic or heterophilic interactions. Heterophilic attachments are to other members of the superfamily such as ICAMs and vascular cell adhesion molecules (VCAMS). During early development of the central nervous system, cells at the roof of neural tube express high levels of NCAMs on their cell surface and are unable to move because of intercellu­lar adhesions. Future neural crest cells lose their NCAMs and begin migrating to various areas of the body. Members of the immunoglobulin superfamily also play a role in the homing process of leukocytes during inflammation.

In summary, body cells are organized into four basic tissue types: epithelial, connective, muscle, and nervous. The ep­ithelium covers and lines the body surfaces and forms the functional components of glandular structures. Epithelial tis­sue is classified into three types according to the shape of the cells and the number of layers that are present: simple, strat­ified, and pseudostratified. The cells in epithelial tissue are held together by four types of intercellular junctions: tight, adhering, gap, and hemidesmosomes. Connective tissue supports and connects body structures; it forms the bones and skeletal system, the joint structures, the blood cells, and the intercellular substances. Adult connective tissue can be divided into four types: loose or areolar, reticular, adipose, and dense (regular and irregular).

Muscle tissue is a specialized tissue designed for contractil­ity. Three types of muscle tissue exist: skeletal, cardiac, and smooth. Actin and myosin filaments interact to produce mus­cle shortening, a process activated by the presence of calcium. In skeletal muscle, calcium is released from the sarcoplasmic reticulum in response to an action potential. Smooth muscle is

often called involuntary muscle because it contracts sponta­neously or through activity of the autonomic nervous system. It differs from skeletal muscle in that its sarcoplasmic reticulum is less defined and it depends on the entry of extracellular cal­cium ions for muscle contraction.

Nervous tissue is designed for communication purposes and includes the neurons, the supporting neural structures, and the ependymal cells that line the ventricles of the brain and the spinal canal.

The extracellular matrix is made up of a variety of proteins and polysaccharides. These proteins and polysaccharides are secreted locally and are organized into a supporting meshwork in close association with the cells that produced them. The amount and composition of matrix vary with the different tis­sues and their function. Extracellular fibers include collagen fibers, which compose tendons and ligaments; elastic fibers, found in large arteries and some ligaments; and thin reticular fibers, which are plentiful in organs that are subject to a change in volume (e.g., spleen and liver).

Cell adhesion molecules are an important set of macro-molecule having a variety of structures and functions. These functions include leukocyte migration into extracellular tissue and integral structural components of several cell-to-cell junc­tions, such as desmosomes. Other adhesion molecules are in­volved in attaching epithelial cells to the underlying connective tissue by way of hemidesmosomes.

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