Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 705

Table 11.8. Endothelial cell junctional molecules in leukocyte transmigration (Source: [ 1449 ]).
Substance CD99 expressed on all leukocytes is also called T-cell surface glycoprotein-E2.
Molecule CD99-like-2 protein (CD99L2) is synthesized in leukocytes and endothelial cells. It
blocks neutrophil transmigration through the perivascular basement membrane,

Type Leukocyte type Stimulus Extravasation

specificity specificity stage

CD99 Transcellular route

CD99L2 Neutrophils Basement membrane crossing

ESAM Neutrophils

ICAM2 IL1 β

JAMa IL1 β Transcellular route

PECAM1 Monocytes, IL1 β Paracellular and

neutrophils, transcellular route

NK cells, some Basement membrane crossing

lymphocyte types

11.5.2.3 Signaling during Extravasation

Rolling

The first step of leukocyte attachment for extravasation is the rolling of leukocytes
over the endothelium owing to selectins. Lymphocytes, eosinophils, neutrophils,
monocytes, and mastocytes utilize selectins as rolling receptors [ 1450 ].
Expression of E-selectin results from cytokines, such as TNF

α , interleukins

IL1 and IL10, oncostatin-M, and lipopolysaccharide. Within 3 to 4 h after

stimulation, E-selectin reaches its maximal level at the plasma membrane [ 1450 ].
On the other hand, interleukin-4 prevents E-selectin production via STAT6 factor.
Glucocorticoids, transforming growth factor-

β

β , and cAMP can counteract cytokine-

induced expression of E-selectin [ 1450 ].
Interleukin-4 and oncostatin-M trigger P-selectin synthesis, but not TNF ,

and LPS [ 1450 ]. L-selectin is constitutively expressed on myeloid cells and a
large subset of lymphocytes. Lymphocyte and neutrophil activation provokes rapid
(within minutes) proteolytic cleavage of L-selectin [ 1450 ]. Various chemoattractants
and activators, such as C5a, fMLP, leukotriene-B4, IL8, TNF, and granulocyte-
macrophage colony-stimulating factor (gmCSF or CSF2), but not gCSF (CSF3),
mCSF (CSF1), IL1, and interferon-

α ,IL1 β

, cause this proteolytic shedding.
Leukocyte clustering of E-selectin is associated with the linkage to the actin
cytoskeleton, as this clustering causes the recruitment of actin-binding proteins,
such as

γ

-actinin, filamin, focal adhesion kinase, paxillin, and vinculin [ 1451 ].
Clustering of P-selectins is also associated with changes in the actin cytoskeleton.
Selectins and their ligands, i.e., carbohydrate structures on glycoproteins
(P-selectin ligands PSGL1 and CD24; L-selectin ligands GlyCAM1, MAdCAM1,

α