Page 154 - Veterinary Immunology, 10th Edition

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Neutrophils are short-lived terminally differentiated cells that have
a limited reserve of energy that cannot be replenished. They are

therefore most active immediately after release from the bone
marrow but are rapidly exhausted and can undertake only a limited
number of phagocytic events. Most neutrophils survive for only a
few days. They die as a result of apoptosis and mononuclear
phagocytes remove the cell corpses. Most such cell death is

physiological, simply removing unwanted, unused cells. As
neutrophils age they express changes in their surface that send an
“eat-me” message to monocytes. For example, the phospholipid

phosphatidyl serine is normally found only on the inner side of the
plasma membrane. As neutrophils age the membrane flips, and
phosphatidyl serine is exposed and recognized by macrophages
that promptly eat the affected cell, a form of cell death called
efferocytosis.

Neutrophil apoptosis also occurs in the presence of inflammatory
stimuli, especially ROS. This may also involve the formation of
NETs of exocytosed DNA. When dendritic cells ingest apoptotic

neutrophils containing bacteria, they secrete TGF-β, IL-6, and IL-23.
As described previously, this IL-23 stimulates the differentiation of
Th17 cells that attract even more neutrophils (Chapter 20).
Conversely, ingestion of uninfected apoptotic neutrophils triggers
the secretion of IL-10 and TGF-β, promoting the production of

regulatory T cells and suppressing inflammation (Chapter 20).
Thus neutrophils may be considered a first line of defense,
converging rapidly on invading organisms and destroying them

promptly but being incapable of sustained effort. The second line of
defense is the mononuclear phagocyte system. DAMPs released by
neutrophil degranulation or death promote the recruitment and
activation of both macrophages and dendritic cells, augmenting
both the innate and adaptive immune responses (see Fig. 2.8).

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