Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 93

peptides such as cathelicidins and nuclear proteins such as histones. Ejection
of mitochondrial DNAs depends on reactive oxygen species and interleukin-5
produced by T H2 cells.

3.7.3 Neutrophils

Neutrophil (N m) has small plasma granules and frequently mul-

tilobed nucleus. Normally, neutrophils account for 50 to 70% of all leukocytes.
Scouting neutrophils look after possible invading agents.
Neutrophils possess an arsenal of hydrolytic and oxidative substances as well as
pore-forming molecules such as pannexins that can cause tissue destruction that can
contribute to further ischemic injury as well as autoimmunity.

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3.7.3.1 Immunostimulatory and Immunosuppressive Neutrophils

Tumors avoid the activity of the immune system, as they set up an immunosuppres-
sive environment. Neutrophils that are major effector cells during inflammation can
also control excessive inflammation, as they secrete anti-inflammatory cytokines.
The neutrophil phenotype is regulated by the acute-phase response protein serum
amyloid-A1. Increased concentration of serum amyloid-A1 observed in tumors
as well as blood renders neutrophils immunosuppressive [ 178 ]. Serum amyloid-
A1 indeed provokes differentiation of neutrophils that release anti-inflammatory
interleukin-10. However, it also fosters the interaction of invariant natural killer T
cells with immunosuppressive neutrophils to limit their suppressive activity, as the
production of IL10 and IL12 is reduced and enhanced, respectively. Therefore, neu-
trophils adopt a pro-inflammatory phenotype. Invariant NKT cells thus counteract
immunosuppression and oppose cancer development [ 178 ].

3.7.3.2 Neutrophils as Scavengers in Cell Necrosis

Neutrophils are rapidly recruited to the site of inflammation, hence responding not
only to microbial infection, but also sterile injury and organ necrosis to contribute to
wound healing. Cell necrosis releases multiple pro-inflammatory damage-associated
molecular patterns (DAMP), or host-derived indicators of cellular damage, such as
proteins, nucleic acids, extracellular matrix components, and lipid mediators. These
DAMPs recruit neutrophils [ 179 ].
Adenosine triphosphate generated from necrotic cells at the injury site activates
the NLRP3 71 inflammasome to assist neutrophils in extravasation across the

71 Or NALP3; NOD-like receptor (NACHT, LRR, and PYD domain-containing) family, pyrin
domain-containing proteins.