scholarly journals CX3CR1 and vascular adhesion protein-1-dependent recruitment of CD16+ monocytes across human liver sinusoidal endothelium

Hepatology ◽  
2010 ◽  
Vol 51 (6) ◽  
pp. 2030-2039 ◽  
Author(s):  
Alexander I. Aspinall ◽  
Stuart M. Curbishley ◽  
Patricia F. Lalor ◽  
Chris J. Weston ◽  
Miroslava Blahova ◽  
...  
Keyword(s):  
Human Liver ◽  
Adhesion Protein ◽  
Sinusoidal Endothelium ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

scholarly journals Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 13
Author(s):  
Raine Toivonen ◽  
Sanja Vanhatalo ◽  
Maija Hollmén ◽  
Eveliina Munukka ◽  
Anniina Keskitalo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hepatic Steatosis ◽  
Visceral Adipose Tissue ◽  
Leukocyte Infiltration ◽  
Fat Accumulation ◽  
Adhesion Protein ◽  
Hepatic Fat ◽  
Vascular Adhesion ◽  
Visceral Adipose ◽  
Vascular Adhesion Protein 1

Toll-like receptor 5 ligand, flagellin, and vascular adhesion protein 1 (VAP-1) are involved in non-alcoholic fatty liver disease. This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected into C57BL/6J (WT) and C57BL/6-Aoc3-/- (VAP-1 KO) mice on a high-fat diet twice a week every 2 weeks for 10 weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration, and lipolysis in visceral adipose tissue. Consequently, an increased release of glycerol led to hepatic steatosis in WT, but not in KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT mice, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

scholarly journals Inhibition of vascular adhesion protein 1 protects dopamine neurons from the effects of acute inflammation and restores habit learning in the striatum

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Serena Becchi ◽  
Alberto Buson ◽  
Bernard W. Balleine
Keyword(s):  
Inflammatory Response ◽  
Functional Decline ◽  
Neuronal Loss ◽  
Dopamine Neurons ◽  
Neural Function ◽  
Adhesion Protein ◽  
Habit Learning ◽  
Inflammatory State ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Abstract Background Changes in dopaminergic neural function can be induced by an acute inflammatory state that, by altering the integrity of the neurovasculature, induces neuronal stress, cell death and causes functional deficits. Effectively blocking these effects of inflammation could, therefore, reduce both neuronal and functional decline. To test this hypothesis, we inhibited vascular adhesion protein 1 (VAP-1), a membrane-bound protein expressed on the endothelial cell surface, that mediates leukocyte extravasation and induces oxidative stress. Method We induced dopaminergic neuronal loss by infusing lipopolysaccharide (LPS) directly into the substantia nigra (SN) in rats and administered the VAP-1 inhibitor, PXS-4681A, daily. Results LPS produced: an acute inflammatory response, the loss of dopaminergic neurons in the SN, reduced the dopaminergic projection to SN target regions, particularly the dorsolateral striatum (DLS), and a deficit in habit learning, a key function of the DLS. In an attempt to protect SN neurons from this inflammatory response we found that VAP-1 inhibition not only reduced neutrophil infiltration in the SN and striatum, but also reduced the associated striatal microglia and astrocyte response. We found VAP-1 inhibition protected dopamine neurons in the SN, their projections to the striatum and promoted the functional recovery of habit learning. Thus, we reversed the loss of habitual actions, a function usually dependent on dopamine release in DLS and sensitive to striatal dysfunction. Conclusions We establish, therefore, that VAP-1 inhibition has an anti-inflammatory profile that may be beneficial in the treatment of dopamine neuron dysfunction caused by an acute inflammatory state in the brain.

scholarly journals Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate

Blood ◽  
2009 ◽  
Vol 114 (26) ◽  
pp. 5385-5392 ◽  
Author(s):  
Elina Kivi ◽  
Kati Elima ◽  
Kristiina Aalto ◽  
Yvonne Nymalm ◽  
Kaisa Auvinen ◽  
...  
Keyword(s):  
Primary Amines ◽  
Leukocyte Trafficking ◽  
Hydrogen Peroxide Production ◽  
Lymphocyte Adhesion ◽  
Adhesion Protein ◽  
Inflammatory Microenvironment ◽  
Inflamed Endothelium ◽  
End Products ◽  
Vascular Adhesion ◽  
Vascular Adhesion Protein 1

Abstract Leukocytes migrate from the blood into areas of inflammation by interacting with various adhesion molecules on endothelial cells. Vascular adhesion protein-1 (VAP-1) is a glycoprotein expressed on inflamed endothelium where it plays a dual role: it is both an enzyme that oxidizes primary amines and an adhesin that is involved in leukocyte trafficking to sites of inflammation. Although VAP-1 was identified more than 15 years ago, the counterreceptor(s) for VAP-1 on leukocytes has remained unknown. Here we have identified Siglec-10 as a leukocyte ligand for VAP-1 using phage display screenings. The binding between Siglec-10 and VAP-1 was verified by different adhesion assays, and this interaction was also consistent with molecular modeling. Moreover, the interaction between Siglec-10 and VAP-1 led to increased hydrogen peroxide production, indicating that Siglec-10 serves as a substrate for VAP-1. Thus, the Siglec-10–VAP-1 interaction seems to mediate lymphocyte adhesion to endothelium and has the potential to modify the inflammatory microenvironment via the enzymatic end products.

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