scholarly journals Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn’s Disease Patients

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Laura Choteau ◽  
Francis Vasseur ◽  
Frederic Lepretre ◽  
Martin Figeac ◽  
Corine Gower-Rousseau ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Functional Activity ◽  
Serine Proteases ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Disease Phenotype ◽  
Mannose Binding ◽  
Antibody Levels ◽  
Binding Lectin

Abstract Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn’s disease and this deficiency is frequently associated with a severe Crohn’s disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn’s disease phenotype in 69 Crohn’s disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin–mannose-associated serine protease (MBL-MASP) functional activity in Crohn’s disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn’s disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn’s disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

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 Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins

2022 ◽  
Vol 18 (1) ◽  
pp. e1010226
Author(s):  
Carolina De Marco Verissimo ◽  
Heather L. Jewhurst ◽  
József Dobó ◽  
Péter Gál ◽  
John P. Dalton ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Fasciola Hepatica ◽  
Membrane Attack Complex ◽  
Mannose Binding Lectin ◽  
Helminth Parasite ◽  
Lectin Pathway ◽  
Mannose Binding ◽  
Carbohydrate Arrays ◽  
Infectious Stage ◽  
Binding Lectin

The complement system is a first-line innate host immune defence against invading pathogens. It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate arrays or microbial liposaccharides, respectively. The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like structure, the membrane attack complex (MAC), on the pathogen surface. We found that the infectious stage of the helminth parasite Fasciola hepatica, the newly excysted juvenile (NEJ), is resistant to the damaging effects of complement. Despite being coated with mannosylated proteins, the main initiator of the Lectin pathway, the mannose binding lectin (MBL), does not bind to the surface of live NEJ. In addition, we found that recombinantly expressed serine protease inhibitors secreted by NEJ (rFhSrp1 and rFhSrp2) selectively prevent activation of the complement via the Lectin pathway. Our experiments demonstrate that rFhSrp1 and rFhSrp2 inhibit native and recombinant MBL-associated serine proteases (MASPs), impairing the primary step that mediates C3b and C4b deposition on the NEJ surface. Indeed, immunofluorescence studies show that MBL, C3b, C4b or MAC are not deposited on the surface of NEJ incubated in normal human serum. Taken together, our findings uncover new means by which a helminth parasite prevents the activation of the Lectin complement pathway to become refractory to killing via this host response, in spite of presenting an assortment of glycans on their surface.

Mannose-binding lectin deficiency is not associated with Anti-Saccharomyces cerevisiae antibody in Korean Crohn's disease patients

2014 ◽  
Vol 429 ◽  
pp. 206-211 ◽  
Author(s):  
You Sun Kim ◽  
Young-Ho Kim ◽  
Byong Duk Ye ◽  
Dong Won Park ◽  
Ji Won Kim ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mannose Binding Lectin ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Components of the Lectin Pathway of Complement in Haematologic Malignancies

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1792
Author(s):  
Maciej Cedzyński ◽  
Anna S. Świerzko
Keyword(s):  
Serine Proteases ◽  
Proteolytic Enzymes ◽  
Alternative Pathway ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Classical Pathway ◽  
Mannose Binding ◽  
Molecular Patterns ◽  
Binding Lectin ◽  
Haematologic Malignancies

The complement system is activated cascadically via three distinct major routes: classical pathway (CP), alternative pathway (AP) or lectin pathway (LP). The unique factors associated with the latter are collectins (mannose-binding lectin, collectin-10, collectin-11), ficolins (ficolin-1, ficolin-2, ficolin-3) and proteins of the mannose-binding lectin-associated serine protease (MASP) family (MASP-1, MASP-2, MASP-3, MAp19, MAp44). Collectins and ficolins are both pattern-recognising molecules (PRM), reactive against pathogen-associated molecular patterns (PAMP) or danger-associated molecular patterns (DAMP). The MASP family proteins were first discovered as complexes with mannose-binding lectin (MBL) and therefore named MBL-associated serine proteases, but later, they were found to interact with ficolins, and later still, collectin-10 and collectin-11. As well as proteolytic enzymes (MASP-1, MASP-2, MASP-3), the group includes non-enzymatic factors (MAp19, MAp44). In this review, the association-specific factors of the lectin pathway with haematologic malignancies and related infections are discussed.

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