Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Cleator, John H.; Zhu, Wen Qin; Vaughan, Douglas E.; Hamm, Heidi E.

doi:10.1182/blood-2004-07-2698

Cited by 96 publications

(96 citation statements)

References 53 publications

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“…The Ca 2ϩ response of endothelial cells leads to enhanced permeability and activation of the endothelial NO synthase enzyme, which results in lowered smooth muscle tone and increased perfusion (45). It also leads to the degranulation of Weibel-Palade bodies, which increases thrombus formation as well as the adhesion of leukocytes and platelets to endothelial cells through von Willebrand factor and P-selectin (46). Taking our novel observations into account, the direct endothelial cell-activating property of MASP-1 may fundamentally contribute to the inherent vascular changes that occur during the inflammatory reaction, in an attempt to control and limit the damage to host tissues.…”

Section: Discussionmentioning

confidence: 99%

Complement Protease MASP-1 Activates Human Endothelial Cells: PAR4 Activation Is a Link between Complement and Endothelial Function

Megyeri

Makó

Beinrohr

et al. 2009

The Journal of Immunology

120

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Activation of the complement system can induce and enhance inflammatory reaction. Mannose-binding lectin-associated serine protease-1 (MASP-1) is an abundant protease of the complement lectin pathway; however, its physiological function is unclear. In this study, we demonstrate for the first time that MASP-1 is able to activate Ca2+ signaling, NF-κB, and p38 MAPK pathways in cultured HUVECs. Activation was initiated by MASP-1 only; the related protease, MASP-2, had no such effect. The phenomenon was dependent on the proteolytic activity of MASP-1, suggesting modulation of endothelial cell function through a protease-activated receptor (PAR). Using synthetic peptide substrates representing the protease-sensitive regions of PARs, we were able to demonstrate that PAR4 is a target of MASP-1. The presence of functionally active PAR4 in HUVECs was demonstrated using PAR4 agonist peptide and mRNA quantification. Finally, we showed that the amount of membrane-bound intact PAR4 decreases after MASP-1 treatment. All of these results provide a novel link between the regulation of endothelial cell function and complement system activation, and they suggest that MASP-1-induced PAR4 activation could contribute to the development of the inflammatory reaction.

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Section: Discussionmentioning

confidence: 99%

Complement Protease MASP-1 Activates Human Endothelial Cells: PAR4 Activation Is a Link between Complement and Endothelial Function

Megyeri

Makó

Beinrohr

et al. 2009

The Journal of Immunology

120

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“…However, at the site of injury and/or infection, MASP-1 may be trapped via the pattern recognition of MBL and ficolins, thus the local concentration may be much higher than its plasma concentration. P-selectin, one of the best-characterized components of Weibel-Palade bodies [16], is released rapidly in response to among others thrombin and histamine by G-protein coupled PARs [37], and by histamine H1 receptors [38], respectively. 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].…”

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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“…For example, Cleator et al have reported that P-selectin and VWF can be differentially released from HUVECs (Cleator et al, 2006). HUVECs stimulated with cAMP or an agonist peptide that binds to protease-activated receptor 2 (PAR2) display a delayed release of VWF and a reduced release of P-selectin compared with HUVECs stimulated with histamine, thrombin, or agonist peptides that bind to PAR1.…”

Section: Variations In Wpbsmentioning

confidence: 99%

Formation and function of Weibel-Palade bodies

Metcalf,

Nightingale,

Zenner

et al. 2008

Journal of Cell Science

134

140

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Weibel-Palade bodies (WPBs) are secretory organelles used for post-synthesis storage in endothelial cells that can, very rapidly, be triggered to release their contents. They carry a variety of bioactive molecules that are needed to mount a rapid response to the complex environment of cells that line blood vessels. They store factors that are essential to haemostasis and inflammation, as well as factors that modulate vascular tonicity and angiogenesis. The number of WPBs and their precise content vary between endothelial tissues, reflecting their differing physiological circumstances. The particular functional demands of the highly multimerised haemostatic protein von Willebrand Factor (VWF), which is stored in WPBs as tubules until release, are responsible for the cigar shape of these granules. How VWF tubules drive the formation of these uniquely shaped organelles, and how WPB density increases during maturation, has recently been revealed by EM analysis using high-pressure freezing and freeze substitution. In addition, an AP1/clathrin coat has been found to be essential to WPB formation. Following recruitment of cargo at the TGN, there is a second wave of recruitment that delivers integral and peripheral membrane proteins to WPBs, some of which is AP3 dependent.

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Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Cited by 96 publications

References 53 publications

Complement Protease MASP-1 Activates Human Endothelial Cells: PAR4 Activation Is a Link between Complement and Endothelial Function

Complement Protease MASP-1 Activates Human Endothelial Cells: PAR4 Activation Is a Link between Complement and Endothelial Function

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

Formation and function of Weibel-Palade bodies

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