Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 698

11.5 Inflammation

The immune system responds to aggression by inflammation, a defensive event
cascade. Inflammation includes: (1) effector and cell delivery to the involved region;
(2) limitation of the damage spreading by a physical barrier; and (3) angiogenesis
and tissue repair.
The major inflammatory events comprise: (1) an immediate local increase in
blood supply with vasodilation upstream and vasoconstriction downstream from the
affected region; (2) a decrease in blood velocity for cell adhesion; (3) an increase
in local capillary permeability, resulting in plasma leakage in affected tissues and
creating interstitial space congestion (the exudated fluid has a higher protein content
than the fluid that is normally filtrated by the capillary wall); (4) an increase in
expression of endothelial adhesion molecules 26 for cell adhesion and extravasation;
and (5) an influx of phagocytic cells into damaged tissues. 27

Later, lymphocytes

enter the inflammation site.
Leukocyte chemotaxis under molecular guidance is controlled by external and
internal signals that activate signal transduction cascades and regulate the cytoskel-
eton dynamics (Vol. 2 - Chap. 6. Cell Motility). Several signaling pathways are
involved in sensing chemoattractant gradient and amplification, among which is the
phosphatidylinositol 3-kinase axis.
In addition to migration of leukocytes during inflammation, cell subpopulations
continuously patrol organ microvasculature at rest to search for invading particles.
Subpopulations of monocytes permanently scout the skin, mesentery, and brain
microcirculation. Upon infection, they are the very first cells to enter tissue.
Intravascular CD1d-restricted invariant natural killer T cells patrol within liver
sinusoids at a speed of 10 to 20 m/min [ 1444 ]. Vascular patrolling CSF1R + ,

Ly6g (in Mus musculus) monocytes are also able to extravasate [ 1445 ].

Vascular inflammation is detected by augmented circulating interleukin-6 that is
produced by activated inflammatory cells within the vessel wall. Synthesis of IL6,
in turn, causes the expression of hepatic acute-phase reactants, such as C-reactive
protein,

−

γ -fibrinogen, and angiotensinogen [ 1446 ].

11.5.1 Extravasation

Alarm signals generated at inflammatory foci reach the vascular lumen to attract
diverse leukocyte subsets that decipher and integrate these signals. Soluble factors,
i.e., cytokines, chemokines, chemoattractants, and adhesion molecules as well
as adhesion and chemotactic receptors in both endothelial cells and leukocytes,
orchestrate various steps of leukocyte recruitment during inflammation. Cytokines

26 Endothelial cells, activated by released IL1 and TNF, express VCAM, ICAM1, E-selectin, and
L-selectin. Mastocytes release histamine and prostaglandin, macrophages TNF α and IL1.

27 Neutrophils, followed by macrophages, are the first leukocyte type to migrate.