Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 538

Table 9.25. Main types of heparan sulfate proteoglycans (HSPG). The major plasmalemmal
HSPGs are the glycosylphosphatidylinositol-anchored glypicans and transmembrane syndecans.
Perlecan, agrin, and collagen-18 are the principal species in the extracellular matrix, especially
basement membranes (Source: [ 924 ]).

Location Function

Syndecan-1 Monocytes, macrophages, L-selectin ligand

neutrophils, eosinophils, Chemokine receptor

lymphocytes, platelets, Signaling

Endothelial cells

Syndecan-2 Macrophages, endothelial cells

Glypican Endothelial cells, macrophages

Perlecan Basement membrane, Growth factor reservoir

interstitial matrix

Collagen-18 Basement membrane, L-selectin ligand

interstitial matrix Growth factor reservoir

Agrin Basement membrane, Growth factor reservoir

interstitial matrix

Rolling of flowing blood cells is affected by the hemodynamic forces applied
at the wetted surface of the vessel wall. The rolling mainly involves selectins.
Hemodynamic forces can favor an extended conformation of certain domains of
the selectin structure and thereby strengthen selectin-ligand bonds [ 984 ]. 103
During inflammation, resident macrophages produce cytokines, such as tumor-
necrosis factor, which quickly induce appearance of preformed P- and E-selectins
on the wetted surface of endothelial cells. Interactions between P-selectins and
leukocyte ligands, such as P-selectin glycoprotein ligand PSGL1, initiates rolling on
the endothelium. Rolling is stabilized when formation of new downstream receptor-
ligand bonds balance dissociation of upstream bonds. Rolling is further stabilized
by L-selectin binding to heparan sulfate proteoglycans on the endothelial wetted
surface. 104
Heparan sulfate proteoglycans participate in almost every stage of leukocyte
diapedesis (Table 9.25 ). Like L-selectin, leukocyte

α M β 2 -integrin binds to heparan
sulfate proteoglycans. They also present heparan sulfate-bound chemokines, such
as CXCL8 produced by tissue-resident macrophages, to chemokine receptors on
leukocytes. Chemokine binding activates leukocyte integrins; a stable interaction is
then formed between leukocytes and endothelial cells.

103 Lectin and epidermal growth factor-like domains of P-selectin show both curved and extended
conformations. The extended configuration increases the affinity of P-selectin for its ligand
P-selectin glycoprotein-1. It also enhances rolling adhesion on L-selectin under shear flow.
104 The 3 selectin types interact with mucins produced by the endothelium. However, heparan
sulfate proteoglycans are the dominant L-selectin ligand on the inflamed endothelium during acute
inflammation.