Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 726

Diapedesis requires transient disassembly of endothelial junctions. Monomeric
Rac, Rap1 and RhoA GTPases, focal adhesion kinases, protein kinase-C, and
phosphatidylinositol 3-kinase promote leukocyte extravasation. Extravasation de-
pends on basement membrane composition: leukocytes cross vascular basement
membranes that contain laminin-8. 62 The interstitial matrices remodel during
inflammation with an increased production of fibronectin, tenascin, collagen,
and sulfated proteoglycans. Peptidases and glycosaminoglycan-degrading enzymes
are upregulated shortly after transendothelial migration by inflammatory cells to
penetrate the extracellular matrix.
The strong neutrophil inflammatory response can damage host tissues. 63 Any
anti-inflammation therapy must target the infiltrated immunocytes translated in
effectors of inflammatory diseases without too much disturbance of the migration
and function of leukocytes required in immunity. Effective therapies target specific
immunocytes and focus on particular chemical reactions involved in chemotaxis and
cell motion. 64 Recruitment of T H1 cells in T H1 -based inflammation disorders, such
as atherosclerosis, can be targeted.

11.6 Healing

Repair of damaged tissues involves blood cells and molecules to seal the vessel
wall gap off, clean the wound, and reconstruct tissues. Various intra- and in-
tercellular mechanisms are activated and coordinated to restore homeostasis and
tissue integrity. Blood coagulation, immune system, and inflammation are primed.
Wound repair usually occurs with a similar sequence of events after exposure to a
destructive agent whatever tissue (e.g., myocardial infarction and skin wound) and
cause.
Delayed wound healing occurs in patients with diabetes or after radiation
exposure. Excessive healing that manifests by deposition of large amounts of
extracellular matrix and alterations in local vascularization and cell proliferation
leads to hypertrophic and keloid scars. In some circumstances, healing leads to
fibrosis. Fibrotic healing prevents tissue regeneration.

62 Leukocytes cannot migrate through a basement membrane that contains laminin-10.
63 Inflammatory diseases can target any body tissue, but they mainly damage target organs or
tissues, such as the skin, intestine, central nervous system, skeleton articulations, respiratory
conduits, and arteries.
64 Blockade of neutrophil chemokine receptors CXCR1 and CXCR2 hinders the neutrophil flux.