Ch. 5: Connective Tissue

Elastin molecules are rich in what amino acids? This gives elastin molecules what structural confirmation?

- glycine, proline, and lysine -much of the protein a random-coil conformation (like that of natural rubber).

What allows integins to have certain specificity to different EMC ligands?

-All are heterodimers with two transmembrane polypeptides: the α and β chains. -Great diversity in the subsets of integrin α and β chains which cells express allows cells to have different specific ECM ligands

What is a type of connective tissue that is broadly classified based off the amount of collagen present?

-Connective Tissue Proper

___________ has similar components as loose connective tissue, but with what differences? What is the responsibility of a major component of this type of tissue?

-Dense connective tissue -with fewer cells, mostly fibroblasts, and a clear predominance of bundled type I collagen fibers over ground substance -the abundance of collagen here protects organs and strengthens them structurally

What is the importance of lysine residues in elastin subunits?

-During deposition on microfibrils the enzyme lysyl oxidase converts the paired lysines' amino groups to aldehydes. -Oxidized lysines on two different elastin molecules then condense as a desmosine ring that acts as a covalent cross-link between the polypeptides, which maintain their rubberlike properties picture: The diagram shows a small piece of an elastic fiber, in two conformations. Elastin polypeptides, the major components of elastic fibers, have multiple random-coil domains that straighten or stretch under force, and then relax. Most of the cross-links between elastin subunits consist of the covalent, cyclic structure desmosine, each of which involves four converted lysines in two elastin molecules. This unusual type of protein cross-link holds the aggregate together with little steric hindrance to elastin movements. These properties give the entire network its elastic quality.

Compare elastic fibers to collagen type I fibers.

-Elastic fibers are thinner -form sparse networks interspersed with collagen bundles in many organs

Where do mast cells originate from?

-From bone marrow precursor cells that circulate in blood and pass through of venules into connective tissue and differentiate.

___________ is the principal component of the fetal umbilical cord, where it is referred to as __________. What is it's composition like? What tissue is this type similar to?

-Mucoid (or mucous) connective tissue -Wharton's jelly -abundant ground substance composed chiefly of hyaluronan -sparse collagen fibers and scattered fibroblasts -Included among the fibroblastic cells are many mesenchymal stem cells -similar to the tissue found in the vitreous chambers of eyes and pulp cavities of young teeth.

_________ are lymphocyte-derived, antibody-producing cells. Describe the appearance of these cells in more detail.

-Plasma cells -relatively large, ovoid cells -have basophilic cytoplasm rich in RER and a large Golgi apparatus near the nucleus that may appear pale in routine histologic preparations -nucleus generally spherical and eccentrically placed -Many of these nuclei contain compact, peripheral regions of heterochromatin alternating with lighter areas of euchromatin -for picture: (b) Plasma are often more abundant in infected tissues, as in the inflamed lamina propria shown here. A large pale Golgi apparatus (arrows) at a juxtanuclear site in each cell is actively involved in the terminal glycosylation of the antibodies (glycoproteins). Plasma cells leave their sites of origin in lymphoid tissues, move to connective tissue, and produce antibodies that mediate immunity. (X400 PT)

__________ is characterized by abundant fibers of type III collagen forming a delicate network that supports various types of cells. This collagen is also known as ______ and is produced by modified fibroblasts often called ________. What happens once these cells secrete the product necessary for the fibers found in this tissue?

-Reticular tissue -reticulin -reticular cells -they remain associated with and partially cover the fibers

What are some functions of adipocytes?

-Storage of lipids as neutral fats -production of heat -cushion and insulate organs and skin

What is a observable significance seen in a particular cell structure and the fibers found in dense regular connective tissue?

-The elongated nuclei of the fibrocytes run parallel with the collagen fibers.

Distinct levels of fibroblast activity can be observed histologically. Explain.

-There are active and quiescent fibroblastic cells: typically referred to as fibroblast and fibrocyte, respectively. Fibroblast -abundant and irregularly branched cytoplasm -contains much RER and Golgi -large ovoid, euchromatic nucleus -prominent nucleolus Fibrocyte (the arrows in the picture) -smaller -spindle-shaped -more heterochromatic -less RER

Describe the appearance and properties of collagen fibers in various types of microscopy .

-When they fill the ECM (eg, in tendons or the sclera of the eye), bundles of collagen appear white -highly regular orientation of subunits makes collagen fibers birefringent with polarizing microscopy Light Microscopy, fibers are acidophillic and stain: -pink with eosin -blue with Mallory trichrome stain -red with Sirius red -Because collagen bundles are long and tortuous, their length and diameter are better studied in spread preparations rather than sections

Proteoglycans consist of what?

-a core protein to which are covalently attached various numbers and combinations of the sulfated GAGs

Glycosaminoglycans (GAGs) are also called what? What are they made of?

-also called mucopolysaccharides -long polymers of repeating disaccharide units

What are macrophages derived from? What does this transformation involve?

-bone marrow precursor cells: monocytes -Monocytes are in the blood and pass though the endothelial lining of blood vessels into the tissues and mature into macrophages -transformation involves increases in cell size, increased protein synthesis, and increases in the number of Golgi complexes and lysosomes.

Reticular fibers consist mainly of what? Describe the structure of these fibers and histological staining properties.

-collagen type III -extensive network (reticulum) of extremely thin (diameter 0.5-2 μm), heavily glycosylated fibers -don't stain well with H&E -argyrophilic (stain black with impregnation of silver salts) -periodic acid-Schiff (PAS) positive - contain up to 10% carbohydrate as opposed to 1% in most other collagen fibers -picture: In these silver-stained sections of adrenal cortex (a) and lymph node (b), networks of delicate, black reticular fibers are prominent. These fibers serve as a supportive stroma in most lymphoid and hematopoietic organs and many endocrine glands. The fibers consist of type III collagen that is heavily glycosylated, producing the black argyrophilia. Cell nuclei are also dark, but cytoplasm is unstained. X100.

Describe the main types of collagens associated with fibrillar collagens. What are a few structures that are partially formed by fibrillar collagens?

-collagen types I, II, and III, have polypeptide subunits that aggregate to form large fibrils clearly visible in the electron or light microscope -Collagen type I, the most abundant and widely distributed collagen, forms large, eosinophilic bundles usually called collagen fibers -often densely fill the connective tissue, forming structures such as tendons, organ capsules, and dermis

What degrades collagen in the ECM and what family does it belong to? How does it work? Where are they made and secreted?

-collagenases -belong to family of matrix metalloproteinases (MMPs) -clip collagen fibrils or sheets in such a way that they are then susceptible to further degradation by nonspecific proteases -Various MMPs are secreted by macrophages and play an important role in remodeling the ECM during tissue repair

How does dense regular connective tissue differ from dense irregular connective tissue? What advantage does this offer? What are some examples of where dense regular connective tissue is found?

-consists mostly of type I collagen bundles and fibroblasts aligned in parallel -great resistance to prolonged or repeated stresses from the same direction examples -strong and flexible tendons, cords connecting muscles to bones -aponeuroses, which are sheet-like tendons -ligaments, bands or sheets that hold together components of the skeletal system

Classification of connective or supporting tissues. Table organized by categories which include (name, general organization, main function, examples).

-cut off in the picture is: bone blood

Other proteoglycans include ________, with very few GAG side chains that binds the surface of type I collagen fibrils, and ________, with an integral membrane core protein providing an additional attachment of ECM to cell membranes.

-decorin -syndecan

In ____________ bundles of collagen fibers appear randomly interwoven, with no definite orientation. What function does this serve? Give some examples where this is found.

-dense irregular connective tissue -tough three-dimensional collagen network provides resistance to stress from all directions -deep dermis layer of skin and capsules surrounding most organs

Though dense regular connective tissue is found in tendons and ligaments, what other type of connective tissue is also found in these structures?

-dense irregular connective tissue on the outer surface of tendons and ligaments that is continuous with the outermost layers of the adjacent muscles and bones

Elastin resists digestion by most proteases, but it is hydrolyzed by what? Where is it made?

-elastase -pancreas

What is the role of elastic fibers in large blood vessels and what kind of structures do they form?

-elastin also occurs as fenestrated sheets called elastic lamellae

All connective tissues originate from what? Where does this tissue mainly develop?

-embryonic mesenchyme -the mesoderm of the developing embryo

Elastic fibers (and lamellae) are a composite of ___________ embedded in a larger mass of cross-linked ________. What are these components secreted by? What are the steps involved in elastic fiber assembly?

-fibrillin microfibrils -elastin -fibroblast (and smooth muscle cells in vascular walls) 1. microfibrils with diameters of 10 nm form from the protein fibrillin (350 kDa) and from several other glycoprotein 2.microfibrils act as scaffolding upon which elastin is deposited in the second step of elastic fiber formation 3.Elastin accumulates between the microfibrils, surrounding most of these, and eventually comprises most of the elastic fiber Picture: Stages in the formation of elastic fibers can be seen by TEM. (a) Initially, a developing fiber consists of many 10-nm- diameter fibrillin microfibrils composed of molecular subunits secreted by fibroblasts and smooth muscle cells. (b) Elastin is deposited on the scaffold of microfibrils, forming growing, amorphous composite structures. The elastin molecules are also secreted by the fibroblasts and quickly become cross-linked into larger assemblies. (c) Elastin accumulates and ultimately occupies most of the electron-dense center of the single elastic fiber shown here. Fibrillin microfibrils typically remain at the fiber surface. Collagen fibrils, seen in cross section, are also present surrounding the elastic fiber. All X50,000.

Briefly describe the functions of ground substance.

-fills space between cells and fibers in connective tissue -allows diffusion of small molecules -because it is viscous, acts as both a lubricant and a barrier to the penetration of invaders

Integrin-microfilament complexes are clustered in fibroblasts and other mesenchymal cells to form structures called ___________ that can be seen by TEM or immunocytochemistry.

-focal adhesions

Fibroblasts are targets of many families of proteins called ___________ that influence cell growth and differentiation. What is fibroblast differentiation like in adults?

-growth factors -in adults, differentiation is rare, though seen in organ repair

In both developing and mature connective tissues, core proteins and GAGs (especially __________) of many proteoglycans serve what function?

-heparan sulfate -bind and sequester various growth factors and other signaling proteins -These proteoglycans are degraded during the early phase of tissue repair and the stored growth factors are then released, which then help stimulate new cell growth and ECM synthesis

Their _______ forces GAGs to an ________ conformation and causes them to sequester _________ as well as water. These features provide GAGs with what kind of functions?

-high negative charge -extended -cations -space-filling, cushioning, and lubricant functions.

Briefly describe what ground substance is and is composed of.

-highly hydrated (with much bound water), transparent, complex mixture of three major kinds of macromolecules: 1. glycosaminoglycans (GAGs) 2. proteoglycans 3. multiadhesive glycoproteins.

The largest and most ubiquitous GAG is __________. What is it's composition? What is a unique feature of this GAG compared to most? This GAG forms what, giving it what kind of importance?

-hyaluronan (also called hyaluronate or hyaluronic acid) -very long polymer of the disaccharide glucosamine-glucuronate -synthesized directly into the ECM by an enzyme complex, hyaluronan synthase, located in the cell membrane of many cells -forms a viscous, pericellular network which binds a considerable amount of water, giving it an important role in allowing molecular diffusion through connective tissue and in lubricating various organs and joints

Embryonic mesenchyme is very rich in what? What function does this serve?

-hyaluronan and water -producing the characteristic wide spacing of cells and a matrix ideal for cell migrations and growth

Release of certain chemical mediators stored in mast cells promotes the allergic reactions known as what? Explain how this occurs. Why can this be dangerous?

-immediate hypersensitivity reactions -see picture: the first step though is that the cells have to be sensitized already, meaning they must already have IgE's specific to the particular antigen. -anaphylactic shock may occur due to this response

Water in the ground substance of connective tissue is referred to as __________ and has an ion composition similar to that of blood plasma. What else does it contain?

-interstitial fluid -also contains plasma proteins of low molecular weight that pass through the thin walls of the smallest blood vessels, the capillaries

In TEM, what features are observed macrophages and what do these features relate to?

-irregular surface with pleats, protrusions, and indentations, features related to their active pinocytotic and phagocytic activities -also generally have a well developed golgi complex and many lysomsomes

When adequately fixed for histologic analysis, what happens to it's components and what does it look like when viewed?

-it components aggregate as fine, poorly resolved material that appears in TEM preparations as electron-dense filaments or granules

An example of a multiadhesive glycoproein is the large (200-400 kDa), trimeric glycoprotein _________. What is it's function? Where is it found?

-laminin -binding sites for integrins, type IV collagen, and specific proteoglycans, providing adhesion for epithelial and other cells -all basal and external laminae are rich in laminin, which is essential for the assembly and maintenance of these structures

The water drawn back into the capillaries is often (more/less) than what is pushed out. (Pick one). What happens subsequently because of this?

-less -excess fluid does not normally accumulate in connective tissue but drains continuously into lymphatic capillaries that eventually return it to the blood

Explain events that trigger inflammation and how this is advantageous to leukocytes, macrophages, and mast cells.

-local release of chemical mediators from various cells, the ECM, and blood plasma proteins -substances act on local blood vessels, mast cells, macrophages, and other cells to induce events characteristic of inflammation -some of these events include: --increased blood flow and vascular permeability --entry and migration of leukocytes --activation of macrophages for phagocytosis

Mast cell granules display what kind of property in terms of dyes? What does this mean? Why do they display this?

-metachromasia -Because of the high content of acidic radicals in their sulfated GAGs -they can change the color of some basic dyes (eg, toluidine blue) from blue to purple or red

multiadhesive glycoproteins all have what? What are they composed of and what does this allow?

-multiple binding sites for cell surface integrins and for other matrix macromolecules -The adhesive glycoproteins are large molecules with branched oligosaccharide chains and allow adhesion of cells to their substrate

What are fibroblasts involved in wound healing called and what is a special feature found in them?

-myofibroblast -have well developed contractile function and enriched with actin.

Occurring in connective tissue of many organs, mast cells are especially numerous where? What is suggested by their locations?

-near small blood vessels in skin and mesenteries (perivascular mast cells) -in the tissue that lines digestive and respiratory tracts (mucosal mast cells) -granule content of the two populations differs somewhat -suggested that they are strategically placed to detect invasion of microorganisms

What are the staining properties of elastic fibers like?

-not strongly acidophilic and stain poorly with H&E -they are stained more darkly than collagen in other stains such as orcein and aldehyde fuchsin -picture: Elastic fibers or lamellae (sheets) add resiliency to connective tissue. Such fibers may be difficult to discern in H&E-stained tissue, but elastin has a distinct, darker-staining appearance with other staining procedures. (a) The length, diameter, distribution, and density of dark elastic fibers are easily seen in this spread preparation of nonstretched connective tissue in a mesentery. X200. Hematoxylin and orcein. (b) In sectioned tissue at higher magnification, elastic fibers can be seen among the acidophilic collagen bundles of dermis. X400. Aldehyde fuchsin. (c) Elastic lamellae in the wall of the aorta are more darkly stained, incomplete sheets of elastin between the layers of eosinophilic smooth muscle. X80. H&E.

Where are elastic fibers typically found

-organs, particularly those subject to much bending or stretching

What is a key proteoglycan found in epithelial tissue?

-perlecan is the key proteoglycan in all basal laminae

Where are reticular fibers typically found?

-produced by fibroblasts occur in the reticular lamina of basement membranes -typically also surround adipocytes, smooth muscle and nerve fibers, and small blood vessel

What difference is observed in proteoglycans compared to glycoproteins?

-proteoglycans have attached GAGs which often comprise a greater mass than the polypeptide core

Where is reticular tissue found? What does it allow for?

-provides a framework with specialized microenvironments for cells in hemopoietic tissue and some lymphoid organs (bone marrow, lymph nodes, and spleen) -resulting cell-lined system creates a meshwork for the passage of leukocytes and lymph. Macrophages and dendritic cells (also in the mononuclear phagocyte family) are also dispersed within these reticular tissues to monitor cells formed there or passing through and to remove debris

Describe linking/anchoring collagens.

-short collagens that link fibrillar collagens to one another (forming larger fibers) and to other components of the ECM -Type VII collagen binds type IV collagen and anchors the basal lamina to the underlying reticular lamina in basement membranes

Delicate reticular networks serve to do what and where? Why are they found at these locations?

-supportive stroma for the parenchymal secretory cells and rich microvasculature of the liver and endocrine glands -Abundant reticular fibers also characterize the stroma of hemopoietic tissue (bone marrow) and some lymphoid organs (eg, spleen and lymph nodes) -because it's where they support rapidly changing populations of proliferating cells and phagocytic cells

The cytoplasm in what kind of cells is hard to distinguish under a slide? Why?

-tendinocytes -difficult to distinguish in H&E-stained preparations because it is very sparse and has acidophilia like that of the collagen

What is a defining feature of collagens?

-triple helix formation of three α chains (happens in the ER). -stabilized by disulfide bonds at their carboxyl terminals

Describe network or sheet-forming collagens.

-type IV collagen (one type found in network or sheet-forming collagens), have subunits produced by epithelial cells -major structural proteins of external laminae and all epithelial basal laminae

Describe mesenchymal cells

-undifferentiated and have large nuclei, with prominent nucleoli and fine chromatin. They are often said to be "spindle-shaped," with their scant cytoplasm extended as two or more thin cytoplasmic processes

Name a few properties of the protein family of collagens.

-various extracellular fibers, sheets, and networks -extremely strong and resistant to normal shearing and tearing forces -key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells -most abundant protein in the human body, representing 30% of its dry weight -major product of fibroblasts (also secreted by several other cell types) -distinguishable by their molecular compositions, morphologic characteristics, distribution, functions, and pathologies

What are the three main fibers found in connective tissue? What are these fibers typically formed from generally?

1. Collagen - proteins of the collagen family 2. Elastic - mainly the protein elastin 3. Reticular - proteins of the collagen family

What are the three categories of collagen fibers and the main types of associated with the particular category?

1. Fibrillar collagens -notably collagen types I, II, and III 2. Network or sheet-forming collagens -such as type IV collagen 3. Linking/anchoring collagen -Type VII collagen

What are the two main forces that act on water in capillaries?

1. Hydrostatic Pressure -caused by the pumping action of the heart -forces water out across the capillary wall 2. Osmotic Pressure -produced by plasma proteins such as albumin -draws water back into the capillaries

1. ______________ is a common tissue, forming a layer beneath the epithelial lining of many organs and filling the spaces between fibers of muscle and nerve. 2. What is another name for this kind of tissue? 3. What is contained in this tissue? 4. What are the most numerous type of cells found in this tissue? 5. What fiber's are found in this tissue, and in whats kind of abundance? 6. What kind of physical properties does this tissue display?

1. Loose connective tissue 2. Areolar Tissue 3. cells, fibers, and ground substance in roughly equal parts 4. fibroblast, but also other connective tissue cells along with nerves and small blood vessels 5. Collagen predominates, but elastic and reticular fibers are found 6. delicate consistency; flexible; not very resistant to stress

Besides hyaluronan, what are four features of GAGs?

1. Smaller (10-40 kDa) 2. sulfated 3. bound to proteins (as parts of proteoglycans), 4. synthesized in Golgi complexes

What are the steps involved in collagen synthesis?

1. The procollagen α chains are produced on polyribosomes of the RER and translocated into the cisternae. These typically have long central domains rich in proline and lysine; in type I collagen every third amino acid is glycine. 2. Hydroxylase enzymes in the ER cisternae add hydroxyl (-OH) groups to some prolines and lysines in reactions that require O2, Fe2+, and ascorbic acid (vitamin C) as cofactors. 3. Glycosylation of some hydroxylysine residues also occurs, to different degrees in various collagen types. 4. Both the amino- and carboxyl-terminal sequences of α chains have globular structures that lack the gly-X-Y repeats. In the RER the C-terminal regions of three selected α chains (α1, α2) are stabilized by cysteine disulfide bonds, which align the three polypeptides and facilitates their central domains folding as the triple helix. With its globular terminal sequences intact, the trimeric procollagen molecule is transported through the Golgi apparatus, packaged in vesicles and secreted. 5. Outside the cell, specific proteases called procollagen peptidases remove the terminal globular peptides, converting the procollagen molecules to collagen molecules. These now self-assemble (an entropy-driven process) into polymeric collagen fibrils, usually in specialized niches near the cell surface. 6. Certain proteoglycans and other collagens (eg, types V and XII) associate with the new collagen fibrils, stabilize these assemblies, and promote the formation of larger fibers from the fibrils. 7. Fibrillar structure is reinforced and disassembly is prevented by the formation of covalent cross-links between the collagen molecules, a process catalyzed by lysyl oxidase.

1. One of the best studied proteoglycans is what? 2. What is its composition? 3. What does it typically interact with? 4. Where is it typically found and what function does it serve?

1. aggrecan, is very large (250 kDa) 2. has a core protein heavily bound with chondroitin and keratan sulfate chains 3. A link protein joins aggrecan to hyaluronan 4. Abundant in cartilage, aggrecan-hyaluronan complexes fill the space between collagen fibers and cells and contribute greatly to the physical properties of this tissue

The four major GAGs found in proteoglycans are?

1. dermatan sulfate 2. chondroitin sulfates 3. keratan sulfate 4. heparan sulfate

1. Another glycoprotein, ______________, is a 235-270 kDa dimer synthesized largely by fibroblasts, with binding sites for collagens and certain GAGs, and forms insoluble fibrillar networks throughout connective tissue. 2. This glycoprotein provides specific binding sites for __________. 3. What are two functions that this glycoprotein is responsible for?

1. fibronectin (L. fibra, fiber + nexus, interconnection) 2. integrins 3. important both for cell adhesion and cellular migration through the ECM

How do proteoglycans come to be and eventually find their way into the ECM? This is a similar process to what kind of component also found in the ECM

1. synthesized in the RER 2. mature in the golgi apparatus (GAG side-chains are added) 3. secreted from cells by exocytosis -similar process to glycoproteins

Describe the hierarchy of the structure of type I collagen

As seen in the figure: 1. Rodlike triple-helix collagen molecules, each 300-nm long, self-assemble in a highly organized, lengthwise arrangement of overlapping regions. 2. The regular, overlapping arrangement of subunits continues as large collagen fibrils are assembled. 3. This structure causes fibrils to have characteristic cross striations with alternating dark and light bands when observed in the EM. 4. Fibrils assemble further and are linked together in larger collagen fibers visible by light microscopy. 5. Type I fibers often form into still larger aggregates bundled and linked together by other collagens.

These two tissues are often closely associated, with the two types grading into each other and making distinctions between them somewhat arbitrary

Dense irregular and loose connective tissues

What is a significant observation seen in regards to the amino acid sequence in type 1 collagen?

Every third amino acid is glycine

The major constituent of connective tissue is?

Extracellular matrix (ECM)

What is the most common cell found in connective tissue proper? Describe.

Fibroblast -Synthesize and secrete collagen (most abundant protein of body) and elastin

Mast cells function in the localized release of many bioactive substances important in what functions? Name and describe 6 of these bioactive substances and briefly describe what they do.

Heparin, a sulfated GAG that acts locally as an anticoagulant Histamine, which promotes increased vascular permeability and smooth muscle contraction Serine proteases, which activate various mediators of inflammation Eosinophil and neutrophil chemotactic factors, which attract those leukocytes Cytokines, polypeptides directing activities of leukocytes and other cells of the immune system Phospholipid precursors, which are converted to prostaglandins, leukotrienes, and other important lipid mediators of the inflammatory response.

Other white blood cells besides macrophages and plasma cells normally comprise a population of wandering cells in connective tissue are known as what?

Leukocytes

__________ have highly developed phagocytic ability and specialize in turnover of protein fibers and removal of dead cells, tissue debris, or other particulate material, being especially abundant at sites of inflammation.

Macrophages

_______ are oval or irregularly shaped cells of connective tissue, between 7 and 20 μm in diameter, filled with basophilic secretory granules

Mast cells

Extracellular matrices consist of different combinations of ________ and ________. Give a few examples of both.

Protein fibers -collagen and elastic fibers Ground Substance -complex of anionic, hydrophilic proteoglycans, glycosaminoglycans (GAGs), and multiadhesive glycoproteins (laminin, fibronectin, and others)

What happens to most of the secreted ECM components

Undergo further modification outside the cell before assembling as matrix

Give an example of a common fate of a proteoglycan after being secreted.

become bound to the hyaluronan by link proteins and their GAG side-chains associate further with collagen fibers and other ECM components

What is the term used to describe the process by which particular molecules attract particular cells, such as leukocytes to infected tissues

chemotaxis

What is something that plays a role in the diversity seen among proteoglycans.

enzymatic differences in the Golgi complexes

The long polymer repeating disaccharide units in GAGs are usually what?

hexosamine -can be glucosamine or galactosamine uronic acid -can be glucuronate or iduronate

Where are macrophages typically present

in the stroma of most organs

Collagen and elastin form what?

large fibers, as well as the GAGs, proteoglycans, and multiadhesive glycoproteins that comprise the ground substance