Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 94

vascular endothelium using integrins [ 179 ] (Vol. 3 - Chap. 11. Receptors of the
Immune System). 72 The NLRP3 inflammasome promotes maturation and secretion
of interleukin-1 , reactive oxygen

species, and thioredoxin-interacting protein, thereby acting as a sensor for metabolic
stress, such as in insulin resistance and type-2 diabetes mellitus [ 180 ]. Maturation
of IL1

β . It can integrate signals from interleukin-1 β

into an active form is actually controlled by caspase-1-activating platforms,
the so-called inflammasomes. In addition, formyl peptides released from necrotic
cells guide neutrophils to the injury site [ 179 ].

β

3.7.3.3 Neutrophils as Microphages for Pathogens

Neutrophils constitute a first line of defense against invading pathogens. These
polymorphonuclear microphages are able to phagocytize foreign cells, toxins, and
viruses. Neutrophils use neutrophil extracellular traps that consist of chromatin
coated with peptidases, such as myeloperoxidase, elastase, and cathepsin-G, to trap
and kill bacteria [ 97 ].
Neutrophils express numerous receptors for bacterial phagocytosis, such as
α M β 2 -integrin that binds complement component C3b on the surface of opsonized
bacteria and IgG Fc receptors (Fc

R) that bind IgG-coated particles and immune
complexes [ 97 ]. These molecules facilitate the uptake of opsonized bacteria into
phagosomes. Phagosomes then fuse with lysosomes and neutrophil granules that
contain numerous proteolytic and antibacterial enzymes and peptides. NADPH
oxidase of phagolysosome membranes generates reactive oxygen species to destroy
bacteria.
Human neutrophil peptides are released from granules of activated leukocytes
to kill pathogens. Human neutrophil peptides can also modulate inflammation and
vascular tone. In endothelial cells stimulated by human neutrophil peptides, COx2
expression (but not COx1) increases in time- and dose-dependent manner [ 181 ].
However, human neutrophil peptides do not significantly enhance COx2 activity,
hence PGI2 production, but provoke the release of endothelin-1.

γ

3.7.3.4 Neutrophil Migration

Neutrophils are the first recruited cells and responders to sites of inflammation and
infection by primary chemoattractants. They then attract other cells, as they release
secondary (relay) chemoattractants such as leukotriene-B4 that enables neutrophil
activation and migration [ 182 ]. 73

72 Extracellular ATP is an NLRP3-activating DAMP that is released on cell injury or necrosis. It
stimulates rapid K + efflux from P2X 7 receptor, an ATP-gated ion channel, and triggers gradual
recruitment and pore formation by the pannexin-1 hemichannel [ 180 ].
73 Leukotriene-B4 amplifies cAMP production, myosin-2 phosphorylation, F actin polymerization,

and cell polarization.