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APOPTOSIS
Apoptosis is a physiologic type of programmed cell
death that is essential for normal development and reg-
ular life of tissues and organs. It is used by multicellular
organisms for elimination of “unwanted” cells, which
may include excess and unnecessary cells, defective,
senescent, and harmful cells. Any apoptosis disorder
potentially leads to diseases. By contrast to necrosis,
which is a nonphysiologic accidental cell death resulting
from irreversible cell injury, apoptosis takes place
according to a genetic cell-suicide programme and is an
active process initiated by external signals or intrinsic
events, such as DNA-damage or irreparable stress at cel-
lular organelles. Both pathways that initiate and regulate
apoptosis, the death receptor pathway and the mito-
chondrial pathway, lead to the activation of particular
proteases called caspases (cysteine aspartic acid-specific
proteases). A cascade of caspase-mediated cleavage
processes takes place causing dramatic cellular changes,
which give rise to the characteristic morphological
apoptosis patterns. The cells lose plasma membrane
asymmetry and surface differentiations and round up.
DNA-fragmentation leads to a chromatin hyperconden-
sation and a kind of “explosion” of the cells results in
the appearance of “apoptotic bodies”, which are phago-
cytosed by surrounding cells.
Panel A shows typical apoptotic bodies originating
from human lymphocytes undergoing programmed cell
death after irradiation. The bodies are rounded, but they
show intact plasma membranes and contain remnants
of the cell nucleus and organelles. The hypercondensed
chromatin (asterisk) is present in multiple nuclear frag-
ments and, due to chromatin collapse against the
nuclear periphery often appears in the shape of a ces-
cent, as shown in the body at the right hand side of the
micrograph. Cleavage of the nuclear DNA hallmarks
apoptosis and causes the most severe damage to the
cells.
A large number of results indicate that cells use dif-
ferent ways for active self-destruction. Apoptosis is
referred to a type I of programmed cell death. In anoth-
er type (type II), autophagy has a major role, and cyto-
plasmic constituents are degraded before nuclear
destruction. Recent data suggest that functional links
exist between apoptosis and autophagic cell death. Both
types may occur simultaneously in tissues, and can
coexist in the same cell.
The Nucleus
References
Abraham MC, and Shaham, S (2004) Death without caspases,
caspases without death. Trends Cell Biol 14: 184
Bursch W, Ellinger A, Gerner Ch, and Schulte-Hermann R (2003)
Caspase-independent and autophagic cell death. In: When cells
die (Lockshin R, Zakeri Z, and Tilly JL, eds) New York Chichester
Weinheim Brisbane Singapore Tokyo: Wiley-Liss
Cohen I, Castedo M, and Kroemer G (2002) Tantalizing
Thanatos: unexspected links in death pathways. Trends Cell Biol
12: 293
Cuervo AM (2004) Autophagy: in sickness and in health. Trends
Cell Biol 14: 70
Machamer CE (2003) Golgi disassembly in apoptosis: cause or
effect? Trends Cell Biol 13: 279
Penninger JM, and Kroemer G (2003) Mitochondria, AIF and
caspases – rivalling for cell death execution. Nat Cell Biol 5: 97
Zhang J, and Xu M (2002) Apoptotic DNA-fragmentation and
tissue homeostasis. Trends Cell Biol 12: 84
VIRAL INCLUSIONS
Viruses account for a large number of acute infections
that occur as a consequence of hereditary or acquired
forms of immunodeficiencies. Because of their small
size (20–300 nm), single virus particles can be detected
only by electron microscopy. Some viruses may form
aggregates in the nucleus and/or cytoplasm of the
infected cells. Such viral inclusion bodies may be visible
by light microscopy and definitely by electron
microscopy. Polyoma viruses are ubiquitous in nature
and can often be observed in tubular cells of transplant-
ed kidneys. Panels B and C illustrate such a situation.
The spherical virus particles have a diameter of
30–45 nm and are arranged in characteristic paracrys-
talline arrays (inset in B) that occupy parts of the nucle-
oplasm (B) and cytoplasm (C). Note the difference in
structure between the nuclear viral inclusions and the
nucleolus (Nu in B). Another virus causing combined
nucleo-cytoplasmic inclusions is the cytomegalovirus,
which belongs to the herpesvirus family. Cytomegalo-
virus infections affect multiple organs and are often
observed in immunosuppressed recipients of trans-
plants or in AIDS patients.
References
Colvin RB (1998) Renal transplant pathology. In: Heptinstall’s
pathology of the kidney, Jenette J, Olson J, and Schwartz M (eds).
Philadelphia: Lippincott-Raven, pp 1409
Magnification: x 6,800 (A); x 10,000 (B, C); x 32,000 (inset)