Biomedical Engineering Reference
In-Depth Information
phagosomes mature by a progression of fusion and fission events that are
regulated and directional, with certain combinations that are permitted and
others that are not. For example, an early endosome and a lysosome would
not be allowed to fuse together (Mayorga
et al.,
1991). For a particle to be
ingested it must first bind to the surface of the phagocytic cell, antibodies
that have bound to microorganisms are recognised by receptors on the cell
surface. Binding of antibody to macrophage or neutrophil receptors induces
the cell to engulf the attached particle and form a phagosome.
4.1. Association of Annexins with Phagosomes
Most studies of annexins in this context have focused on neutrophils,
with some additional documentation regarding annexins in dendritic cells.
Phagocytosis in neutrophils is accompanied by degranulation, caused by
fusion of either phagosomes or the plasma membrane with cytoplasmic
granules. Degranulation is discussed earlier in section 2. Dendritic cells
express annexins I, III, IV, V and VI with expression higher in immature
than mature dendritic cells (Larsson
et al.,
1995). The localization of den-
dritic cell annexins to the plasma membrane could be a consequence of
their being deposited there following exocytosis, or they may be targeted
to this site in readiness for some role in phagocytosis (Larsson
et al.,
1997).
But in the absence of any clear data derived from experiments using living
cells, it is equally likely that these annexins could participate in a cellular
activity completely unrelated to either endocytosis or exocytosis.
During phagocytosis of
Mycobacterium tuberculosis
(the H37Ra
attenuated strain) in human neutrophils, Majeed
et al.
(1998) observed that
annexins 111, IV and VI translocated from the cytoplasm to the vicinity of
phagosomes, whilst no change was seen in the localization of annexins I or
V. Annexin IV translocation occurred both in Ca
2+
depleted neutrophih as
well as neutrophils cultured in the absence of external Ca
2+
. During exter-
nal binding and envelopment of H37Ra there is an increase in [Ca
2+
]
i
which
most likely is an important part of the translocation of these annexins.
Depletion of intracellular Ca
2+
in neutrophils allows more of the invading
mycobacteria to survive showing that Ca
2+
-dependent activities are an
important part of the degradative process. The association of these annex-
ins to the membranes of phagosomes appears to promote fusion of these
vesicles with azurophils and specific granules. These intracellular fusion
events are essential for the killing and digestion of microorganisms.
The relationship between annexins and phagosomes may depend on
the contents of, or the type of phagosome, suggesting that neutrophils may
have the capacity to regulate and dimiminate the contents of their phago-
somes. Thus, Larsson
et al.
(Larsson
et al.,
1997) followed the uptake of
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