Page 41 - Textbook of Pathology, 6th Edition
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i) fibrillar structural proteins (collagen, elastin);  25
                                                               ii) adhesion proteins (fibronectin, laminin, fibrillin,
                                                               osteonectin, tenacin); and
                                                               iii) molecules of proteoglycans and glycosaminoglycans
                                                               (heparan sulphate, chondroitin sulphate, dermatan sulphate,
                                                               keratan sulphate, hyaluronic acid).                    CHAPTER 3
                                                                  CAMs participate in fertilisation, embryogenesis, tissue
                                                               repair, haemostasis, cell death by apoptosis and in
                                                               inflammation. CAMs may be detected on the surface of cells
                                                               as well as free in circulation. There are 5 groups of CAMs:
                                                               i) Integrins. They have alpha (or CD11*) and beta (CD18)
                                                               subunits and have a role in cell-ECM interactions and in
                                                               leucocyte-endothelial cell interaction.
                                                               ii)  Cadherins. These are calcium-dependent adhesion
                                                               molecules which bindadjacent cells together and prevent
                                                               invasion of ECM by cancer cells. Various types of cadherins
           Figure 3.4  Diagrammatic representation of the intercellular
           junctions.                                          include: E-cadherin (epithelial cell), N-cadherin (nerve cell),
                                                               M-cadherin (muscle cell), and P-cadherin (placenta).
           cells. As a result, the regions of occluding zones are  iii) Selectins. Also called as lectins, these CAMs contain  Cell Injury and Cellular Adaptations
           impermeable to macromolecules. The examples of occluding  lectins or lectin-like protein molecules which bind to
           zones are seen in renal tubular epithelial cells, intestinal  glycoproteins and glycolipids on the cell surface. Their major
           epithelium, and vascular endothelium in the brain   role is in movement of leucocytes and platelets and develop
           constituting blood-brain barrier.                   contact with endothelial cells. Selectins are of 3 types:
                                                               P-selectin (from platelets, also called CD62), E-selectin (from
           2. Adhering junctions (Zonula adherens).  These are located
           just below the occluding zones between the adjacent cells  endothelial cells, also named ECAM), and L-selectin (from
           and are permeable to tracer particles. These zones are in  leucocytes, also called LCAM).
           contact with actin microfilaments e.g. in small cell carcinoma  iv) Immunoglobulin superfamily. This group consists of a
           of the lung.                                        variety of immunoglobulin molecules present on most cells
                                                               of the body. These partake in cell-to-cell contact through
           3. Desmosomes (Macula  densa).  These are tiny adhesion
           plates present focally between the adjacent epithelial cells,  various other CAMs and cytokines. They have a major role
           especially numerous in the epidermis. Bundles of    in recognition and binding of immunocompetent cells. This
           intermediate filaments (termed tonofilaments in the case of  group includes ICAM-1,2 (intercellular adhesion molecule,
           epidermis) project from the intercellular desmosomes and  also called CD54), VCAM (vascular cell adhesion molecule,
           radiate into the cytoplasm. Hemidesmosomes are a variant  also named CD106), NCAM (neural cell adhesion molecule).
           of desmosomes, occurring at the basal region of epithelial  v)CD44. The last group of adhesion molecules is a break
           cells between plasma membrane and the basement      away from immunoglobulin superfamily. CD44 molecule
           membrane.                                           binds tohyaluronic acid and is expressed on leucocytes. It
                                                               is involved in leucocyte-endothelial interactions as well
           4. Gap junctions (Nexus).  Gap junctions or nexus are the
           regions on the lateral surfaces of epithelial cells where the  as in cell-ECM interactions.
           gap between the adjoining plasma membranes is reduced  2. CYTOKINES. Another way the cells may communicate
           from 20 nm to about 2 nm in width. Pits or holes are present  with each other is by release of peptides and other molecules
           in the regions of gap junctions so that these regions are  acting as paracrine function. Cytokines are soluble proteins
           permeable to small tracer particles.                secreted by haemopoietic and non-haemopoietic cells in
                                                               response to various stimuli. Their main role is in activation
           Molecular Interactions between Cells                of immune system. Presently, about 200 cytokines have been
                                                               identified which are grouped in 6 categories:
           Besides having intercellular junctions, most cells
           communicate at molecular level as follows:          i) Interferons (IFN)
           1. Cell adhesion molecules (CAMs)                   ii) Interleukins (IL)
           2. Cytokines                                        iii) Tumour necrosis factor group (TNF, cachectin)
                                                               iv) Transforming growth factor (TGF)
           3. Membrane receptors
                                                               v) Colony stimulating factor (CSF)
           1. CELL ADHESION MOLECULES (CAMs).  These are       vi) Growth factors (e.g. platelet-derived growth factor PDGF,
           chemicals which mediate the interaction between cells (cell-  epidermal growth factor EGF, fibroblast growth factor FGF,
           cell interaction) as well as between cells and extracellular
           matrix (cell-ECM interaction). The  ECM is the ground  *CD number (for Cluster of Differentiation) is the nomenclature given to
           substance or matrix of connective tissue which provides  the clone of cells which carry these molecules on their cell surface or in
           environment to the cells and consists of 3 components:  their cytoplasm.
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