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Connective Tissue Components
Cells: fibroblasts, macrophages, mast cells (plus resident cells (osteocytes), and non-resident cells (leukocytes))
Fibers: collagen, elastic, reticular
Ground substance: water, GAGs, proteoglycans, glycoproteins (electrolyte control, compression allowance)
Types of General Connective Tissues
Loose (areolar): randomly arranged, lots of ground substance
-lamina propria of GI tract, submucosa of trachea
Dense Irregular: fibers run in different directions (mostly collagen Type I)
-capsules, dermis
Dense Regular: fibers run in same direction (mostly collagen Type I)
-tendons, some ligaments
-lung, arteries
Reticular (collagen Type III)
Type of Special Connective Tissues
Synthesizes collagen, elastic & reticular fibers
Synthesizes complex carbs of ground substance
Appear as long, pale, oval nucleus
Has flat, elongated processes
Macrophage (AKA Histiocyte)
Derived from monocyte
Secretion of products controlled by phagocytosis, immune complexes, complement, signals from lymphocytes
Engages in phagocytosis of bacteria and cell debris
MHCII displayed on surface (presents antigen to CD4+ helper cells)
-termed antigen presenting cells (APCs)
May fuse to create foreign body giant cells (Langerhans cells)
Appear as large cells with small indented nuclei
Mast Cell
Contain basophilic granules
Surface displays high affinity Fc receptors (degranulate in response to IgE)
2 types:
1. MCTC contain chymase and tryptase (skin)
2. MCT contain only tryptase (lungs and intestinal mucosa)
Not found in connective tissue surrounding brain and spinal cord
Secretions increase vascular permeability, mucus secretion and viscosity, and smooth muscle contraction in bronchioles (involved in hypersensitivity reactions)
Granules of Mast Cells
Histamine: increases permeability of small blood vessels
Heparin: anti-coagulant
Serine proteases:
-tryptase: marker of mast cell activation
-chymase: generates angiotensin II in response to vascular tissue injury (includes apoptosis of vascular smooth muscle)
ECF and NCF: attract eosinophils and neutrophils
Synthesized after activation:
-leukotrienes (LTC4 > LTD4 + LTE4): trigger prolonged constriction of smooth muscle in airways
-tumor necrosis factor alpha (TNFα): cytokine that increases expression of adhesion molecules
-interleukins, growth factors, prostaglandin D2
Molecular Structure of Collagen Fibril
Alpha Chain: 3 polypeptides form right-handed triple helix (every 3rd AA is glycine, followed by proline, preceded by hydroxyproline or hydroxylysine)
Triple helix is considered collagen molecule AKA tropocollagen (300nm long and 1.5nm in diameter)
Collagen fibril is composed of staggered collagen molecules (creates overlap zones and hole zones)
Collagen fibril displays banding (68nm btw ea. band)
Classes of Collagens
Fibrillar collagens: glycine - proline - hydroxyproline
-I, II, III, V, XI
FACITs: interruptions in triple helixes that allow flexibility
Hexagonal network-forming collagens
Transmembrane collagens
-XIII (focal adhesion), XVII (hemidesmosome), XXIII (metastatic cancer cells), XXV (brain specific)
Multiplexins: triple helix domains and interruptions
Basement membrane forming collagens
-IV, VI (beaded filament), VII (anchoring fibrils)
Reticular Fibers
Thin and branched in meshwork pattern (hairnet)
Composed of collagen Type III
Found at epithelial/connective tissue interface and around adipocytes, small blood vessels, nerves, and muscles
Formed by fibroblasts, reticular cells (modified fibroblasts), Schwann cells, or smooth muscle cells
Elastic Fibers
Thin, yellow
Yield easily to stretching due to central core of elastin and fibrillin microfibrils
-elastin: lots of proline, glycine, and valine; no hydroxylysine; random glycines allow random coiling due to hydrophobia; contains desmosine and isodesmosine that covalently bond molecules to each other
-fibrillin-1: glycoprotein that forms microfibrils
Found in elastic ligaments (ligamentum flava & nuchae), vocal cords, larynx
Formed by fibroblasts and smooth muscle cells
Elastic fibers of blood vessels have no fibrillin
Composition of Extracellular Matrix
Structural fibers and proteins
Ground substance:
-multiadhesive glycoproteins
Functions of Extracellular Matrix
Mechanical and structural support
Biochemical barrier (ions, plasma proteins, etc.)
Regulates metabolic function of surrounding cells
Regulates cell and molecular migration
Organizes water
Anchors cells within tissue
Binds and retains growth factors
Glycosaminoglycans (GAGs)
Covalently bound to proteoglycans
Most abundant in ground substance
Composed of repeating disaccharide units
High negative charge (sulfate groups) attracts and organizes water
-chondroiton-4 sulfate
-chondroiton-6 sulfate
-dermatan sulfate
-keratan sulfate
-heparan sulfate
Hyaluronan (AKA hyaluronic acid)
Very long, rigid GAG
Synthesized on cell surface (not post-translationally modified)
Contains no sulfate
Does not link to proteins (doesn't form proteoglycan), but can form proteoglycan aggregates via link proteins that bind proteoglycans to it
Regulates distribution and transport of plasma proteins (dense network keeps macromolecules from diffusing)
Composes of GAGs covalently attached to core protein
Multiadhesive Glycoproteins
Stabilize ECM and link it to cell surface
Regulate and modulate functions of ECM related to cell movement and migration and stimulate cell proliferation and differentiation
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