scholarly journals A New Surface Plasmon Resonance Assay for In Vitro Screening of Mannose-Binding Lectin Inhibitors

2016 ◽  
Vol 21 (7) ◽  
pp. 749-757 ◽  
Author(s):  
Matteo Stravalaci ◽  
Daiana De Blasio ◽  
Franca Orsini ◽  
Carlo Perego ◽  
Alessandro Palmioli ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Ischemia Reperfusion ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
In Vitro Screening ◽  
Mannose Binding ◽  
Binding Lectin

Mannose-binding lectin (MBL) is a circulating protein that acts as a soluble pattern recognition molecule of the innate immunity. It binds to carbohydrate patterns on the surface of pathogens or of altered self-cells, with activation of the lectin pathway of the complement system. Recent evidence indicates that MBL contributes to the pathophysiology of ischemia-reperfusion injury and other conditions. Thus, MBL inhibitors offer promising therapeutic strategies, since they prevent the interaction of MBL with its target sugar arrays. We developed and characterized a novel assay based on surface plasmon resonance for in vitro screening of these compounds, which may be useful before the more expensive and time-consuming in vivo studies. The assay measures the inhibitor’s ability to interfere with the binding of murine MBL-A or MBL-C, or of human recombinant MBL, to mannose residues immobilized on the sensor chip surface. We have applied the assay to measure the IC50 of synthetic glycodendrimers, two of them with neuroprotective properties in animal models of MBL-mediated injuries.

scholarly journals Pharmacological inhibition of mannose-binding lectin ameliorates neurobehavioral dysfunction following experimental traumatic brain injury

2016 ◽  
Vol 37 (3) ◽  
pp. 938-950 ◽  
Author(s):  
Daiana De Blasio ◽  
Stefano Fumagalli ◽  
Luca Longhi ◽  
Franca Orsini ◽  
Alessandro Palmioli ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Surface Plasmon Resonance ◽  
Brain Injury ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Mannose Binding Lectin ◽  
Brain Injured ◽  
Mannose Binding ◽  
Traumatic Brain Injured ◽  
Binding Lectin

Mannose-binding lectin is present in the contusion area of traumatic brain-injured patients and in that of traumatic brain-injured mice, where mannose-binding lectin-C exceeds mannose-binding lectin-A. The reduced susceptibility to traumatic brain injury of mannose-binding lectin double knock-out mice (mannose-binding lectin−/−) when compared to wild type mice suggests that mannose-binding lectin may be a therapeutic target following traumatic brain injury. Here, we evaluated the effects of a multivalent glycomimetic mannose-binding lectin ligand, Polyman9, following traumatic brain injury in mice. In vitro surface plasmon resonance assay indicated that Polyman9 dose-dependently inhibits the binding to immobilized mannose residues of plasma mannose-binding lectin-C selectively over that of mannose-binding lectin-A. Male C57Bl/6 mice underwent sham/controlled cortical impact traumatic brain injury and intravenous treatment with Polyman9/saline. Ex-vivo surface plasmon resonance studies confirmed that Polyman9 effectively reduces the binding of plasma mannose-binding lectin-C to immobilized mannose residues. In vivo studies up to four weeks post injury, showed that Polyman9 induces significant improvement in sensorimotor deficits (by neuroscore and beam walk), promotes neurogenesis (73% increase in doublecortin immunoreactivity), and astrogliosis (28% increase in glial fibrillary acid protein). Polyman9 administration in brain-injured mannose-binding lectin−/− mice had no effect on post-traumatic brain-injured functional deficits, suggestive of the specificity of its neuroprotective effects. The neurobehavioral efficacy of Polyman9 implicates mannose-binding lectin-C as a novel therapeutic target for traumatic brain injury.

Characterization of the recognition of Candida species by mannose-binding lectin using surface plasmon resonance

The Analyst ◽  
2013 ◽  
Vol 138 (8) ◽  
pp. 2477 ◽  
Author(s):  
Sébastien Damiens ◽  
Pierre Marie Danze ◽  
Anne-Sophie Drucbert ◽  
Laura Choteau ◽  
Thierry Jouault ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Candida Species ◽  
Mannose Binding Lectin ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Michael Osthoff ◽  
Marten Trendelenburg
Keyword(s):  
Endothelial Dysfunction ◽  
Renal Dysfunction ◽  
Serine Proteases ◽  
Vascular Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Increased Risk ◽  
Mannose Binding ◽  
Binding Lectin

Contrast-induced nephropathy (CIN) is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL), a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R) injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.

scholarly journals Dual and Opposite Costimulatory Targeting with a Novel Human Fusion Recombinant Protein Effectively Prevents Renal Warm Ischemia Reperfusion Injury and Allograft Rejection in Murine Models

2021 ◽  
Vol 22 (3) ◽  
pp. 1216
Author(s):  
Jordi Guiteras ◽  
Laura De Ramon ◽  
Elena Crespo ◽  
Nuria Bolaños ◽  
Silvia Barcelo-Batllori ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Recombinant Protein ◽  
Reperfusion Injury ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Warm Ischemia ◽  
Solid Organ ◽  
Inflammatory Models

Many studies have shown both the CD28—D80/86 costimulatory pathway and the PD-1—PD-L1/L2 coinhibitory pathway to be important signals in modulating or decreasing the inflammatory profile in ischemia-reperfusion injury (IRI) or in a solid organ transplant setting. The importance of these two opposing pathways and their potential synergistic effect led our group to design a human fusion recombinant protein with CTLA4 and PD-L2 domains named HYBRI. The objective of our study was to determine the HYBRI binding to the postulated ligands of CTLA4 (CD80) and PD-L2 (PD-1) using the Surface Plasmon Resonance technique and to evaluate the in vivo HYBRI effects on two representative kidney inflammatory models—rat renal IRI and allogeneic kidney transplant. The Surface Plasmon Resonance assay demonstrated the avidity and binding of HYBRI to its targets. HYBRI treatment in the models exerted a high functional and morphological improvement. HYBRI produced a significant amelioration of renal function on day one and two after bilateral warm ischemia and on days seven and nine after transplant, clearly prolonging the animal survival in a life-sustaining renal allograft model. In both models, a significant reduction in histological damage and CD3 and CD68 infiltrating cells was observed. HYBRI decreased the circulating inflammatory cytokines and enriched the FoxP3 peripheral circulating, apart from reducing renal inflammation. In conclusion, the dual and opposite costimulatory targeting with that novel protein offers a good microenvironment profile to protect the ischemic process in the kidney and to prevent the kidney rejection, increasing the animal’s chances of survival. HYBRI largely prevents the progression of inflammation in these rat models.

Mannose-binding lectin genetics: from A to Z

2008 ◽  
Vol 36 (6) ◽  
pp. 1461-1466 ◽  
Author(s):  
Peter Garred
Keyword(s):  
Epidemiological Studies ◽  
Mannose Binding Lectin ◽  
Host Cells ◽  
Lectin Pathway ◽  
Mannose Binding ◽  
The Stability ◽  
Genetically Determined ◽  
Micro Organisms ◽  
Binding Lectin

MBL (mannose-binding lectin) is primarily a liver-derived collagen-like serum protein. It binds sugar structures on micro-organisms and on dying host cells and is one of the four known mediators that initiate activation of the complement system via the lectin pathway. Common variant alleles situated both in promoter and structural regions of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variations in MBL serum concentrations influence the susceptibility to and the course of different types of infectious, autoimmune, neoplastic, metabolic and cardiovascular diseases, but this is still a subject under discussion. The fact that these genetic variations are very frequent, indicates a dual role of MBL. This overview summarizes the current molecular understanding of human MBL2 genetics.

scholarly journals ON VASCULAR STENOSIS, RESTENOSIS AND MANNOSE BINDING LECTIN

2016 ◽  
Vol 29 (1) ◽  
pp. 57-59 ◽  
Author(s):  
Barbara Stadler KAHLOW ◽  
Rodrigo Araldi NERY ◽  
Thelma L SKARE ◽  
Carmen Australia Paredes Marcondes RIBAS ◽  
Gabriela Piovezani Ramos ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mannose Binding Lectin ◽  
Mannose Binding ◽  
Vascular Stenosis ◽  
Micro Organisms ◽  
The Complement System ◽  
Binding Lectin

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

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