Connective tissue extracellular matrix types

Fig. 49.1. An overview of connective tissue extracellular matrix. Supporting the epithelial cell layer is a basal lamina, beneath which are collagen, elastic fibers, and proteoglycans. The cell types present in connective tissue, such as fibroblasts and macrophages, have been removed from the diagram for clarity.

Connective tissue, such as tendon and cartilage, differs from other solid tissues In that most of Its volume Is made up of extracellular matrix rather than cells. This matrix Is packed with Insoluble protein fibers and contains proteoglycans, various multladhesive proteins, and hyaluronan, a very large, nonsulfated GAG. The most abundant fibrous protein In connective tissue Is collagen. Rubberlike elastin fibers, which can be stretched and relaxed, also are present In deformable sites (e.g., skin, tendons, heart). As discussed later, the fibronectins, a family of multladhesive matrix proteins, form their own distinct fibrils In the matrix of some connective tissues. Although several types of cells are found In connective tissues, the various ECM components are produced largely by cells called fibroblasts. 

TGF-Ps are pleiotrophic cytokines. They are capable of inhibiting the cell cycle and, hence, cell growth of several cell types, most notably epithelial and haematopoietic cells. These factors, however, stimulate the growth of other cell types, most notably cells that give rise to connective tissue, cartilage and bone. They induce the synthesis of extracellular matrix proteins and modulate the expression of matrix proteases. They also serve as a powerful chemoattractant for monocytes... 

These serine proteases are used to remove pathogens by their hydrolytic activity. They degrade cell membrane proteins and connective tissue matrices by hydrolysis of extracellular matrix proteins such as fibronectin, type IV collagen and laminin, or solubilizing fibrous elastins [55, 56]. Immune cell proteases also are capable of cleaving cytokines, growth hormone, neuropeptides, and procoagulant proteins such as Factors X and V. 

Collagen is the major insoluble fibrous protein in the extracellular matrix and in connective tissue 80-90% of the collagen in the body consists of types 1, It and 111 (Table 12.2). The collagen superfamily consists of at least 20 collagen types, with as many as 38 distinct polypeptide chains and more than 15 additional proteins that have collagen-like domains. 

The normal artery wall is composed of three layers intima, media, and adventita (Figure 20-10). On the luminal side, the intima contains a single layer of endothelial cells. These cells permit passage of water and other substances from blood into tissue cells. On the peripheral side, the intimal layer is surrounded by a fenestrated sheet of elastic fibers (the internal elastic lamina). The middle portion of the intimal layer contains various extracellular components of connective tissue matrix and fibers and occasional smooth cells, depending on the type of artery, and the age and sex of the subject. 

Many of the cells in tissues are embedded in an extracellular matrix that fills the spaces between cells and binds cells and tissue together. In so doing, the extracellular matrix aids in determining the shape of tissues as well as the nature of the partitioning between tissue types. In the skin, loose connective tissue beneath epithelial cell layers consists of an extracellular matrix in which fibroblasts, blood vessels, and other components are distributed (Fig 49.1). Other types of connective tissue, such as tendon and cartilage, consist largely of extracellular matrix, which is principally responsible for their structure and function. This matrix also forms the sheetlike basal laminae, or basement membranes, on which layers of epithelial cells rest, and which act as supportive tissue for muscle cells, adipose cells, and peripheral nerves. 

Collagen, a family of fibrous proteins, is produced by a variety of cell types but principally by fibroblasts (cells found in interstitial connective tissue), muscle cells, and epithelial cells. Type I collagen [collagen(l)], the most abundant protein in mammals, is a fibrous protein that is the major component of connective tissue. It is found in the extracellular matrix (ECM) of loose connective tissue, bone, tendons, skin, blood vessels, and the cornea of the eye. Collagen(l) contains approximately 33% glycine and 21% proline and hydroxyproline. Hydroxyproline is an amino acid produced by posttranslational modification of peptidyl proline residues (see Chapter 7, section V.C., for an earlier introduction to collagen). 

Alterations of the connective tissue composition of the extracellular matrix are an important feature of various inherited and acquired disorders of soft tissue (Miller 1976). This phenomenon is particularly important in the lung in which elasticity is a vital determinant of function. Interstitial collagen is composed of at least two distinct trimeric polypeptide molecules designated as type 1 and type 111 collagens. Type 1 contains two ai(I) chains and one 02 chain, whereas type 111 contains 3 identical a, (HI) chains. Pulmonary fibroblasts produce more type I... 

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