Chemical and Chemoenzymatic Synthesis of Glycopeptide Selectin Ligands Containing Sialyl Lewis X Structures

Pudelko, Maciej; Bull, James A.; Kunz, Horst

doi:10.1002/cbic.201000029

Cited by 27 publications

(19 citation statements)

References 233 publications

(275 reference statements)

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“…Although it plays a role in the inflammatory response by mediating the rolling of leukocytes on the endothelium [38], the most critical function of P-selectin is to facilitate platelet aggregation at the sites of vascular injury [39]. In contrast to P-selectin, E-selectin is an endothelial cellspecific adhesion molecule; it recognizes sugar motifs containing sialyl-Lewis X on leukocytes, and has an important role in the initial step of the endothelium/leukocyte adhesion -leukocyte rolling [40,41]. Eselectin is not detectable on the surface of normally functioning endothelial cells and it is also absent from their cytoplasm; however, upon pro-inflammatory stimuli (e.g.…”

Section: Discussionmentioning

confidence: 99%

Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E‐selectin expression

Jani

Schwaner

Kajdácsi

et al. 2016

Molecular Immunology

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Abbreviation: HUVEC, human umbilical vein endothelial cell; MBL, mannan-binding lectin; MASP, mannan-binding lectin-associated serine protease; PAR, protease-activated receptor. AbstractThe complement system and neutrophil granulocytes are indispensable in the immune response against extracellular pathogens such as bacteria and fungi. Endothelial cells also participate in antimicrobial immunity largely by regulating the homing of leukocytes through their cytokine production and their pattern of cell surface adhesion molecules. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), a complement lectin pathway enzyme, is able to activate endothelial cells by cleaving protease activated receptors, which leads to cytokine production and enables neutrophil chemotaxis. Therefore, we aimed to investigate how recombinant MASP-1 (rMASP-1) can modify the pattern of P-selectin, E-selectin, ICAM-1, ICAM-2, and VCAM-1 adhesion molecules in human umbilical vein endothelial cells (HUVEC), and whether these changes can enhance the adherence between endothelial cells and neutrophil granulocyte model cells (differentiated PLB-985). We found that HUVECs activated by rMASP-1 decreased the expression of ICAM-2 and increased that of E-selectin, whereas ICAM-1, VCAM-1 and P-selectin expression remained unchanged. Furthermore, these changes resulted in increased adherence between differentiated PLB-985 cells and endothelial cells. Our finding suggests that complement MASP-1 can increase adhesion between neutrophils and endothelial cells in a direct fashion. This is in agreement with our previous finding that MASP-1 increases the production of pro-inflammatory cytokines (such as IL-6 and IL-8) and chemotaxis, and may thereby boost neutrophil functions. This newly described cooperation between complement lectin pathway and neutrophils via endothelial cells may be an effective tool to enhance the antimicrobial immune response.

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Section: Discussionmentioning

confidence: 99%

Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E‐selectin expression

Jani

Schwaner

Kajdácsi

et al. 2016

Molecular Immunology

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“…3 subtypes of selectins, characterized through their N-terminal lectin domain, are defined [17, 18]: E-selectin is mainly expressed by activated endothelial cells, whereas endothelium of noninflamed tissue does not express E-selectin. Potent stimuli of E-selectin expression are IL-1 and TNF [19].…”

Section: Adhesion Molecules: Anchors For Lymphocyte Recruitment Tomentioning

confidence: 99%

Mechanisms and Mediators of Inflammation: Potential Models for Skin Rejection and Targeted Therapy in Vascularized Composite Allotransplantation

Hautz

Wolfram

Grahammer

et al. 2012

Clinical and Developmental Immunology

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Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.

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“…[ [141] Um Glycopeptide mit Festphasensynthesen herzustellen, werden folgende drei Strategien am häufigsten verfolgt (Abbildung 11): [142] 1. Konvergente Fragmentkondensation aktivierter Oligosaccharide mit passend geschützten Volllängenpeptiden; 2.…”

Section: Festphasen-glycopeptidsyntheseunclassified

Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese

Hsu

Hung

et al. 2011

Angewandte Chemie

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Kohlenhydrate spielen eine wichtige Rolle bei biologischen Vorgängen. Das Fortschrittstempo der Kohlenhydratforschung ist jedoch relativ langsam, was unter anderem mit der Komplexität der Kohlenhydratstrukturen und dem Fehlen allgemein anwendbarer Synthesemethoden und Verfahren zur Untersuchung dieser Klasse von Biomolekülen zusammenhängt. Jüngste Fortschritte in der Synthese haben ergeben, dass viele dieser Probleme umgangen werden können. In diesem Aufsatz beschreiben wir die Methoden, die entwickelt wurden, um mit den Herausforderungen kohlenhydratvermittelter biologischer Vorgänge umzugehen. Besonderes Augenmerk wird dabei auf die Entwicklung der automatisierten Synthese von Oligosacchariden gerichtet. Darüber hinaus werden auch Kohlenhydrat‐Mikroarrays und Impfstoffe auf Kohlenhydratbasis behandelt.

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Chemical and Chemoenzymatic Synthesis of Glycopeptide Selectin Ligands Containing Sialyl Lewis X Structures

Cited by 27 publications

References 233 publications

Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E‐selectin expression

Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E‐selectin expression

Mechanisms and Mediators of Inflammation: Potential Models for Skin Rejection and Targeted Therapy in Vascularized Composite Allotransplantation

Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese

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