FINE
STRUCTURE OF ALVEOLAR CAPILLARY UNIT
The cellular composition of
the alveolar capillary unit was not recognized until the era of electron
microscopy. Before that time, it was thought that a single membrane separated
blood and air at the level of the terminal airspace. We now know that, even at
its narrowest, the boundary between blood and air is composed of at least two
cell types (the type I alveolar epithelial cell and the endothelial cell) and
extracellular material, namely, the surfactant lining of the alveolar surface,
the basement membranes, and the so-called “endothelial fuzz.” The last is
composed of mucopolysaccharides and proteoglycans (or glycocalyx) that may be
involved in signal transduction, including mechanotransduction or shear stress
at the endothelial surface. Plate 1-27 shows part of a terminal airspace and
cross sections of surrounding capillaries. In humans, the diameter of the
alveoli varies from 100 to 300 μm. The capillary segments are much smaller
in diameter (10-14 μm) and may be separated from each other by even
smaller distances. Each alveolus (there are 300 million alveoli in the adult
human lungs) may be associated with as many as 1000 capillary segments.
The thinness of the cellular
boundary between the blood and the air presents enormous surface area to air on
one side and to blood on the other ( ̴70 m2 for both lungs). Given the paucity of organelles, the cells at this
location likely play mainly passive roles in physiologic and metabolic events
involved in the management of airborne or bloodborne substrates.
Ninety-five percent of the
alveolus is lined by epithelial type I cells. The remaining cells are larger
polygonal type II cells. These two cell types form a complete epithelial layer
sealed by tight junctions. The cellular layer lining the alveoli is remarkably
impermeable to salt-containing solutions, but little is known about specific
metabolic activities of type I alveolar cells. Growing evidence suggests a more
important role in the maintenance of alveolar homeostasis than previously
thought, evidenced by the expression a large number of proteins such as
aquaporin (AQP-5), T1α, functional ion channels, caveolins, adenosine
receptors, and multidrug-resistant genes. Type II cells and endothelial cells
have long been known to play active roles in the metabolic function of the lung
by producing surfactant and processing circulating vasoactive substances,
respectively. In addition, recent research suggests more complex roles for both
of these cell types.
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| ULTRASTRUCTURE OF PULMONARY ALVEOLI AND CAPILLARIES |
Alveolar Cells And
Surface-Active Layer
As illustrated in Plate 1-28,
in addition to being larger, the type II alveolar cell is distinguished from
the type I alveolar cell by having short, blunt projections on the free
alveolar surface and lamellar inclusion bodies. The intracellular origins of
the lamellar bodies (LBs) and the exact mechanism for lipid transport into them are not known with certainty, although
lipid translocation across the LB membrane is facilitated by the ABCA subfamily
of adenosine triphosphate binding cassette transporters. The LB contains the
phospholipid component of surfactant and two small hydrophobic surfactant
polypeptide proteins (SP-B and SP-C) that are coreleased from the type II cell
by a process similar to exocytosis. Two additional components of surfactant (large
hydrophilic proteins SP-A and SP-D) are synthesized and released independent of
LBs.
After release into the
airspace, surfactant forms a lipid monolayer on the alveolar surface, greatly
reducing surface tension. Although surfactant production, release, and
recycling are critical type II cell functions, these cells are now known to
have many additional functions, including repopulation of type I cells,
clearance, repair, migration to areas of lung injury, and host defense
(including the expression of Toll-like receptors). Type II cells also secrete
and respond to an array of cytokines and chemokines and have been shown to
regulate monocyte transmigration across the epithelium.
Alveolar macrophages are migratory cells and, after fixation for microscopy, they are usually
seen free in the alveolar space or closely applied to the surface of type I
cells. Alveolar macrophages are characterized by irregular cytoplasmic
projections and large numbers of lysosomes. Alveolar macrophages are important
in the defense mechanisms of the lungs.
The cellular components of the
blood-air barrier frequently consist only of the extremely flattened extensions
of endothelial cells and type I alveolar cells. In other regions, the wall
contains such cell types as smooth muscle cells, pericytes, fibroblasts, and
occasional mononuclear cells (including plasma cells). Smooth muscle cells are
found around the mouth of each alveolus in humans. Pericytes ensheathed in
base- ment membrane occur around pulmonary alveolar capillaries but less
frequently than on systemic capillaries. The pericytes are characterized by
having finely branched cytoplasmic processes that approach the endothelial cells
and a web of cytoplasmic filaments that run along the membrane close to the
endothelium. Pericytes can be distinguished from fibroblasts in that the latter
are free of a basement membrane sheath.
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| TYPE II ALVEOLAR CELL AND SURFACE-ACTIVE LAYER |
Endothelial Cell Structure
Details of the fine structure
of pulmonary capillary endothelial cells are shown in Plate 1-29. The
endothelium is of the continuous type (not fenestrated), and the cells are
frequently linked by tight junctions. Alveolar epithelial cells and alveolar
capillary endothelial cells are uniquely interactive and highly codependent
during lung development. The ultrastructural features of the capillary
endothelial cell are in keeping with their primary roles as fluid barriers and
gas transfer facilitators. The thickest portion of the cell is in the vicinity
of the nucleus, where the majority of cytoplasmic organelles, such as
mitochondria, Golgi apparatus, rough endoplasmic reticulum, multivesicular
bodies, microtubules, microfilaments, and Weibel-Palade bodies, reside. However,
the more peripheral slender extensions of these cells are practically devoid of
organelles, and may be as thin as 0.1 μm in some regions.
A growing body of evidence
indicates that the endothelium plays a large number of important physiologic
roles at the alveolar level, many of which appear to be mediated by the caveolae
intracellulare. The caveolae are a subset of membrane (lipid) rafts,
present as flask-shaped invaginations of the plasma membrane. When the pulmonary
capillary endothelial cell membrane is freeze fractured, the caveolae appear as
pits on the inner fracture face and as domes on the outer fracture face.
Intramembranous particles, about 80 to 100 Å in diameter, are randomly
scattered on both faces, except in association with caveolae, where they occur
in rings or plaques. These rings correspond to the skeletal rim seen in thin
sections. The intramembranous particles also occur on the curved faces of the
caveola membrane.
The caveolae contain caveolin
proteins, which serve as organizing centers for signal transduction. Caveolin
proteins have cytoplasmic N and C termini, palmitoylation sites, and a scaffolding
domain that facilitates interaction with signaling molecules. Caveolae are
implicated in a wide variety of cell transport events, including transcytosis
and cholesterol trafficking. Many of the caveolae intracellulares directly face
the vascular lumen, but they are also found on the abluminal surface as vesicles,
vastly increasing the surface of the endothelium. The luminal stoma of the
caveola is spanned by a delicate diaphragm composed of a single lamella (by
contrast with the unit membrane construction of the endothelial plasma membrane
and caveola membrane) that helps create a specialized microenvironment within
the caveola.
In addition to the caveolae,
the endothelial surface has numerous fingerlike projections, which are best demonstrated
in scanning electron micrographs. The size (250-350 nm in diameter; 300 to ≥3000
nm long) and density of the projections are such that they may prevent the
formed elements of blood from approaching the endothelial surface and have the
effect of directing an eddy flow of plasma along the cells. Their function is
not entirely known, but they vastly increase the cell surface area for
interaction with soluble elements in the blood.
