Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 699

and chemokines locally released by an inflammatory focus reach the surrounding
endothelium, which becomes activated.
The repertoire of adhesion molecules expressed by different populations of
leukocytes as well as chemoattractants and their receptors determines their recruit-
ment. These molecules follow a spatiotemporal organization at the wetted (luminal)
surface of the vascular endothelium and leukocyte membrane or create chemical
gradients in damaged tissue.
Margination allows circulating leukocytes to move away from the blood stream.
Capture, or tethering, represents the first contact of a leukocyte with the activated
endothelium. During the first steps — tethering and rolling, labile contacts between
leukocytes and activated endothelial cells depend on selectins and their ligands.
Once leukocytes are captured, they transiently adhere to the endothelium and begin
to roll. 28 Rolling allows leukocytes to search for cues such as glycosaminoglycan-
immobilized chemokines on the endothelial surface [ 1445 ]. Trapped chemokines
activate leukocyte chemokine receptors to express leukocyte integrins that bind
endothelial ligands for firm adhesion.
During the transition from rolling to firm adhesion and crawling, leukocytes
undergo a morphological change from round to polarized promigratory shape.
Endothelial cells emit docking microvilli around adhered leukocytes to prevent
their detachment. Leukocyte crawl on the endothelium to find a suitable place for
transmigration. Crawling includes cell polarization with a leading edge (pseudopod)
and a trailing side (uropod), associated with cytoskeletal rearrangement within cell
protrusion and retraction. The contractile force that pulls the uropod results from
stress fibers with linked myosin-2 nanomotor. Afterward, leukocytes migrate across
endothelium if a chemoattractant is present (chemotactic transmigration).
Mechanotaxis, i.e., response to hemodynamical forces, influences crawling. In
the absence of flow, neutrophils crawl in all directions. Once shear is applied,
neutrophils move perpendicularly to exerted shear [ 1444 ].
After transendothelial migration between adjacent endothelial cells (paracellular
passage) or across them (transcellular diapedesis), leukocytes traverse the endothe-
lial basement membrane. They then continue to travel through the extracellular
matrix guided by a chemotactic gradient.

11.5.2 Molecular Basis of Extravasation

When an inflammatory zone occurs, surrounding endothelial cells become activated
by cytokines and chemokines. They increase their content of adhesion molecules
on their luminal surface. Extravasation during inflammation occurs preferentially at
postcapillary venules.

28 During rolling, bonds are formed at the leading edge of rolling cells and broken at the trailing
edge.