Heparan sulfate proteoglycans in extravasation: assisting leukocyte guidance

Johanna, W. A. M. Celie

doi:10.2741/3578

Cited by 53 publications

(42 citation statements)

References 155 publications

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“…Changes in mRNAs encoding several enzymes involved in heparan sulfate biosynthesis have been noted after cytokine stimulation of endothelial cells, 46 which may result in cleavage of the chains or structural changes that result in altered binding of chemokines and cell adhesion molecules. 47,48 Whether these changes are beneficial to the host or merely reflect a pathophysiologic response is unknown.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice

Axelsson

Kang

et al. 2012

Blood

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Neutrophil recruitment and extravasation at sites of inflammation provide a mechanism for host defense. We showed previously that heparan sulfate, a type of sulfated glycosaminoglycan, facilitates neutrophil recruitment based on the reduction of neutrophil infiltration in mice in which the overall sulfation of the chains was reduced by selective inactivation of IntroductionThe inflammatory response, initiated by injury or infection, begins by release of cytokines, such as TNF-␣ and IL-1, from resident macrophages. These effectors stimulate endothelial cells, resulting in the secretion of von Willebrand factor, which aids in platelet recruitment and thrombus formation, and the rapid appearance of P-selectin on the apical (lumenal) face of endothelial cells. P-selectin interacts with its primary ligand, P-selectin glycoprotein ligand-1 expressed on neutrophils, enabling rolling of the cells under blood flow. Chemokines released by resident inflammatory and stromal cells transcytose across the endothelium and bind to the apical surface. Their presentation to rolling leukocytes then activates G-protein-coupled receptors, which in turn activates integrins and causes firm adhesion of the leukocytes to the endothelium. Changes in cell shape and spreading occur followed by transcellular and paracellular extravasation. After entry into tissues, neutrophils release proteases and reactive oxygen species that kill foreign pathogens and prepare the tissue for repair.A large body of evidence suggests the importance of heparan sulfate in inflammation. Cytokines (TNF-␣, IL-1, and others), Land P-selectins, and chemokines bind to therapeutic heparin and purified heparan sulfate. Furthermore, heparin blocks L-and P-selectin in vivo in mice, 1,2 which may explain in part its anti-inflammatory activity in humans. 3 Recently, we showed that mice bearing an endothelial-specific mutation of the biosynthetic enzyme, N-acetylglucosamine N-deacetylase-N-sulfotransferase-1 (Ndst1) exhibit reduced neutrophil extravasation in vivo in several acute inflammatory models. 4 Decreased neutrophil infiltration was partially the result of enhanced rolling velocity in vitro, which correlated with weaker binding of L-selectin to endothelial cells. Inactivation of Ndst1 also resulted in reduced chemokine transcytosis across endothelial cells and reduced presentation on the cell surface. Ndst1-deficient mice exhibit decreased allergen-induced airway hyper-responsiveness and inflammation characterized by a significant reduction in airway recruitment of inflammatory cells (eosinophils, macrophages, neutrophils, and lymphocytes). 5 Heparan sulfate has a complex structure, consisting of variably sulfated disaccharides arranged in clusters, which make up the binding sites for ligands. 6 Ndst1 and other Ndst isoforms catalyze the initial sulfation of subsets of glucosamine residues, creating the substrates for 2-O-sulfation of adjacent uronic acid residues and 6-O-sulfation (and more rarely 3-O-sulfation) of N-sulfoglucosamine units. 7 Thus, inactivation of...

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Section: Discussionmentioning

confidence: 99%

Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice

Axelsson

Kang

et al. 2012

Blood

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“…During the inflammatory response, endothelial HS interacts with L-selectin on passing leukocytes to aid in the initial tethering of leukocytes to the lumenal surface of the endothelium Celie et al 2009). This interaction may depend on the presence of an unusual N-unsubstituted glucosamine unit in HS (Norgard-Sumnicht and Varki 1995) perhaps in combination with fully sulfated domains (Smits et al 2010).…”

Section: Proteoglycans As Adhesion Receptorsmentioning

confidence: 99%

Heparan Sulfate Proteoglycans

Sarrazin¹,

Lamanna²,

Esko

2011

Cold Spring Harbor Perspectives in Biology

1,251

1,238

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“…All of these biological activities undoubtedly influence the proliferation, migration and morphogenesis of endothelial cells (29,30). HSPG play an important role in inflammation since there is evidence that these molecules interact with L-selectin and chemokines (21,31).…”

Section: Introductionmentioning

confidence: 99%