Basement membrane

• Many years ago before the advent of electron microscopy the light microscopy showed that at the interface between connective tissue and other tissues there is a narrow layer of cell-free matrix.

• This was given the name, basement membrane

• It normally contains:

• Glycoproteins• Glycosaminoglycans

• Type IV collagen

• Reticular fibers

• Most commonly the basement membrane is present at the intersurfaces of epithelium and connective tissue

• The term derives from the fact that the first basement membranes to be recognized were those lying underneath the basal cells of surface epithelia.

• Basement membrane can be demonstrated easily histochemically with the light microscope.

• Glycoproteins and polysaccharides give a positive periodic acid-Schiff reaction, and

• the reticular fibers can be revealed with silver stain.

• Basement membrane is non cellular.

• It is a homogeneous sheet of extra-cellular material present under the basal surface of epithelial cells,

• around muscles, nerves, capillaries, and fat cells.

• So basement membrane can be defined as sheet-like structure of extra-cellular matrix that acts as interface between the supporting tissue (connective tissue) and parenchymal tissue or cells (epithelium, muscle cells, nerves, capillaries, adipocytes or fat cells)

• It is typically stained strongly by carbohydrates with PAS method, and for collagen with van Gieson’s stain.

• It is also stained intensely with silver techniques but is relatively poorly demonstrated with eosin in H and E preparations.

• Electron microscopy modified this view, as it was found that the basement membrane is composed of two quiet distinct components:

• Basal Lamina

• Reticular lamina

• The term "basal lamina" is usually used with electron microscopy, while the term "basement membrane" is usually used with light microscopy.

• The structure known as the basement membrane in light microscopy refers to the stained structure anchoring an epithelial layer.

• This encompasses the basal lamina secreted by epithelial cells and typically a reticular lamina secreted by other cells.

• Basal lamina cannot be distinguished under the light microscope, but under the higher magnification of an electron microscope, the basal lamina and lamina reticularis are visibly distinct structures.

• Basal lamina is thin (about 80 nm thick) sheet-like finely fibrilar layer. Its thickness varies from 40 nm to 120 nm.

• It is a layer of filamentous proteins and proteoglycans.

• It is associated closely to the cell surface.

• The main components of basal lamina are:

• Type IV collagen

• Glycoproteins laminin and entactin

• Proteoglycans

• Reticular lamina contains larger fibrils and glycosaminoglycans of extra-cellular matrix.

• It underlies basal lamina and is rich in reticular fibers.

• It is continuous with the connective tissue proper and it is synthesized by connective tissue.

• Basal lamina consists of an electron dense membrane called lamina densa, about 30–70 nm in thickness, and an electron lucent zone called lamina lucida.

• The Lamina Densa, which is made up of type IV collagen fibers; perlecan (a heparan sulfate proteoglycan) coats these fibers

• The Lamina Lucida is made up of laminin, integrins, entactins, and dystroglycans.

• Lamina densa and lamina lucida together make up basal lamina.

• Basement membrane consists of basal lamina and underlying network of reticular collagen (type III) fibrils.

• It is 30 nm in diameter and 0.1–2 micrometer in thickness.

• This type III collagen is of the reticular type, in contrast to the fibrillar collagen found in the extracellular.

• In addition to collagen, this supportive matrix contains intrinsic macromolecular components.

• Lamina Reticularis attached to basal lamina with anchoring fibrils (type VII collagen fibers) and microfibrils (fibrilin) is collectively known as the basement membrane.

• Basal lamina consists of a fibrilar layer called lamina densa which is separated from the plasma membrane of the adjacent cell by a narrow electron-lucent zone, lamina lucida.

• Lamina densa is 20 nm to 50 nm thick.

• In epidermis lamina lucida is crossed by integral plasma membrane proteins and keratinocyte hemidesmosomes are anchored into lamina densa.

• Basal laminae are of almost similar forms but their thickness and molecular composition vary between different tissues.

• Even between crypts and villi of small intestine the basal laminae are different.

• In Descemet’s membrane of cornea, the basal lamina is much thicker.

• Here the regular type IV collagen is replaced by type VIII collagen.

• The basal lamina of neuromuscular junctions contains a haparan sulphate proteoglycan called agrin.

• Agrin plays a part in the clustering of muscle acetylcholine receptors in the plasma membrane at these junctions.

• Basal lamina serves to anchor the overlying epithelial cells and it is produced by these epithelial cells.

• I kidney glomerular basal lamina is unusual in having a lucent zone on both sides of lamina densa.

• Here these lucent zones are lamina rara interna and lamina rara externa (laminae rarae interna and externa).

• In some tissues, the basal lamina separates two layers of cells and there are no intervening typical connective tissue elements (reticular lamina).

• So actually two basal laminae directly join each others and basal lamina becomes thick. Sometimes this is also called basement membrane.

• In the following situations the basal lamina is very thick

• Glomerular membranes of kidney• Thin portions of the lung inter-alveolar

septa • Capsule of the lens of eye• Anterior limiting membrane (Descemet’s

membrane) in cornea• Reichert’s membrane in placenta

• The thickness of basal lamina may change in some pathological conditions such as glomerulonephritis and diabetes.

• The most notable examples of basement membranes is in the glomerular filtration of kidney, by the fusion of the basal lamina from endothelium of glomerular capillaries and the basal lamina of the epithelium of Bowman’s capsule, and

• between the lung alveoli and pulmonary capillaries, by the fusion of the basal lamina of the lung alveoli and of the basal lamina of the lung capillaries, which is where oxygen and CO2 diffusion happens.

• Basal laminae around the muscle fibers and fat cells are sometimes called external laminae.

• The singular is external lamina.

• The functions of basal laminae are:

• They support and anchor the cells

• They act as selective permeable barrier between adjacent tissues

• They stabilize and orient the tissue layers

• They instructive the adjacent tissues

• They determine the polarity of the associated tissues

• They determine the rate of cell division

• They guide the growing cell processes during normal development and tissue repair

• Reticular lamina is always towards the connective tissue and it is produced by the connective tissue. It is composed of bundles of type III filaments embedded in dense matrix of polysaccharides.

• The high concentration of proteoglycans in this zone is responsible for the positive PAS reaction in light microscopic sections.

• Reticular lamina is much reduced or largely absent in the following tissues:

• Around the muscle fibers

• Schwann cells

• Capillary endothelia

• External to reticular lamina, there are thick fibers of type I collagen.

• Basement membrane consists of:

• Basal lamina

• It has following components in sequence

• Lamina lucida or lamina rara interna

• It is electron-lucid layer containing glycoprotein laminin

• Lamina densa

• It is electron-dense layer composed of type IV collagen

• Lamina lucida or lamina rara externa

• It has similar composition to lamina rara interna. Some sources do not consider this a distinct layer

• Lamina Reticularis

• The three above layers of the basal lamina typically sit on top of the reticular lamina, which is synthesized by cells from the underlying connective tissue and contains fibronectin.

• The exception is when two epithelial layers abut one another as in the alveoli of the lungs and glomeruli of the kidneys, in which the basal lamina of one epithelial layer fuses with that of the other

• Anchoring fibrils composed of type VII collagen extend from the basal lamina into the underlying reticular lamina and loop around collagen bundles.

• Although found beneath all basal laminae, they are especially numerous in stratified squamous cells of the skin.

• Basement membrane serves following functions:

• It serves as a semipermeable membrane. Epithelial tissue is nourished by diffusion of food substances from the blood vessels situated in the underlying connective tissue.

• The primary function of the basement membrane is to anchor down epithelium and its loose connective tissue underneath. It connects the epithelial cells to the underlying connective tissue and thus stabilizes the basal ends of the cells. This function is demonstrated clearly in epidermis, where the basement membrane is very well developed.

• Basement membrane also has a profound instructive effect on the adjacent tissues, determining their polarity, rate of cell division, metabolism, movements and repair.

• The basement membrane is also essential for angiogenesis (development of new blood vessels).

• Basement membrane proteins have been found to accelerate differentiation of endothelial cells.

• They also act as pathways for migration and routing of growing cell processes. This function is seen in the regeneration of the cells of peripheral nervous system.

• After injury when basal lamina guides the outgrowth of axons and the establishment of neuromuscular junctions.

• The basement membrane acts as a mechanical barrier, preventing malignant cells from invading the deeper tissues.

• Early stages of malignancy that are thus limited to the epithelial layer by the basement membrane are called carcinoma in situ.

• In many stratified epithelia, the basal plasma membrane of the cells is strongly adherent to the underlying basement membrane at the sites known as hemi-desmosomes. As the name implies, only half of the desmosome is present; only one cell is participating, the second cell being represented by the basement membrane.

• Latest view regarding the development of basement membrane is that almost all components of basement membrane are produced by epithelium or muscle rather than the adjacent connective tissue.

• Some diseases result from the poor functioning of basement membrane.

• The cause can be genetic defects, injuries by the body's own immune system, or other mechanisms.

• Genetic defects or mutations in the collagen fibers of the basement membrane cause Alport syndrome, a form of renal failure.

• A good example of autoimmune disease is Goodpasture syndrome. Here renal basal lamina collagen is targeted by autoantibodies.

• Collagen type IV is autoantigen (target antigen) of autoantibodies in the autoimmune disease Goodpasture syndrome.

• A group of diseases stemming from improper function of basement membrane zone are united under the name epidermolysis bullosa.