Page 134 - Veterinary Immunology, 10th Edition
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production of G-CSF is coordinated with the rate of neutrophil
VetBooks.ir apoptosis. Thus apoptotic neutrophils are removed by
macrophages. These macrophages then produce interleukin-23 (IL-
23) so that, as neutrophils die, IL-23 production increases. IL-23 in
turn promotes IL-17 production by lymphocytes and the IL-17 in
turn stimulates G-CSF production and stem cell activity. As a result,
the rate of neutrophil production matches the rate of their removal.
Toll-like receptors (TLRs) are also expressed on myeloid stem cells.
During microbial infections, pathogen-associated molecular
patterns (PAMPs) such as lipopolysaccharides bind to these TLRs
and trigger production of more neutrophils. TLRs thus provide a
mechanism whereby neutrophil availability increases rapidly in
response to infection. Administration of G-CSF stimulates
neutrophil production. If administered to cattle around the time
they are calving, it will increase neutrophil numbers and as a result
reduce the prevalence of mastitis. A modified form of G-CSF is
currently available for this purpose in dairy cattle (Chapter 41).
Structure
Neutrophils are about 10 to 20 µm in diameter. They have a finely
granular cytosol at the center of which is an irregular sausage-like
or segmented nucleus (Fig. 5.4). The chromatin within the nucleus
is condensed so that neutrophils cannot divide. Electron
microscopy shows three major types of enzyme-rich granules in
their cytosol (Fig. 5.5). Primary (azurophil) granules contain
enzymes such as myeloperoxidase, lysozyme, elastase, β-
glucuronidase, and cathepsin B. Secondary (specific) granules lack
myeloperoxidase but contain lysozyme and collagenase and the
iron-binding protein lactoferrin. Tertiary granules contain
gelatinase. Mature neutrophils have a small Golgi apparatus, some
mitochondria, a few ribosomes, and a little rough endoplasmic
reticulum. Although neutrophil DNA is tightly condensed and they
have a very short life span, they produce many proteins.
Neutrophils express a broad repertoire of PRRs and can respond
dynamically to PAMPs by producing proinflammatory cytokines.
As a result, they are major mediators of innate immunity.
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