Analysis of Activity of Mannan-Binding Lectin, an Initiator of the Lectin Pathway of the Complement System

2016 ◽  
pp. 133-137
Author(s):  
Steffen Thiel
Keyword(s):  
Complement System ◽  
Lectin Pathway ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin

scholarly journals Diabetes Is Associated with Increased Autoreactivity of Mannan-Binding Lectin

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Esben Axelgaard ◽  
Jakob Appel Østergaard ◽  
Steffen Thiel ◽  
Troels Krarup Hansen
Keyword(s):  
Diabetic Nephropathy ◽  
Complement System ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Lectin Pathway ◽  
Urine Albumin ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin

Mannan-binding lectin (MBL) has been reported to be involved in the pathophysiology of diabetic nephropathy. MBL is a pattern-recognition molecule of the innate immune system that initiates the lectin pathway of the complement system upon recognition of evolutionary conserved pathogen-associated molecular patterns or to altered self-tissue. Our group have previously shown direct effects of MBL on diabetes-induced kidney damage, and we hypothesized that MBL may cause autoactivation of the complement system via binding to neoepitopes induced by hyperglycemia. In the present study, we induced diabetes in MBL knockout mice and in wild type C57BL/6J mice by low-dose streptozotocin injection and measured blood glucose and urine albumin-to-creatinine ratio to monitor development of diabetes. After 24 weeks, fluorescently labelled recombinant MBL was injected intravenously in diabetic MBL knockout mice after which the distribution was investigated using in vivo fluorescence imaging. Mice were subjected to in vivo and ex vivo imaging 24 hours after injection. MBL was found to accumulate in the kidneys of diabetic mice as compared to healthy control mice (p<0.0001). These findings support the hypothesis of a significant role of MBL and the complement system in the pathophysiology of diabetic nephropathy.

scholarly journals Human IgA Activates the Complement System Via the Mannan-Binding Lectin Pathway

2001 ◽  
Vol 167 (5) ◽  
pp. 2861-2868 ◽  
Author(s):  
Anja Roos ◽  
Lee H. Bouwman ◽  
Daniëlle J. van Gijlswijk-Janssen ◽  
Maria C. Faber-Krol ◽  
Gregory L. Stahl ◽  
...  
Keyword(s):  
Complement System ◽  
Lectin Pathway ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin

scholarly journals Increased Autoreactivity of the Complement-Activating Molecule Mannan-Binding Lectin in a Type 1 Diabetes Model

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jakob Appel Østergaard ◽  
Marieta Milkova Ruseva ◽  
Talat Habib Malik ◽  
Ingeborg Torp Hoffmann-Petersen ◽  
Matthew Caleb Pickering ◽  
...  
Keyword(s):  
Complement System ◽  
Drug Targets ◽  
Lectin Pathway ◽  
Diabetes Model ◽  
Healthy Control ◽  
End Stage ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Binding Lectin ◽  
Immunofluorescence Intensity

Background. Diabetic kidney disease is the leading cause of end-stage renal failure despite intensive treatment of modifiable risk factors. Identification of new drug targets is therefore of paramount importance. The complement system is emerging as a potential new target. The lectin pathway of the complement system, initiated by the carbohydrate-recognition molecule mannan-binding lectin (MBL), is linked to poor kidney prognosis in diabetes. We hypothesized that MBL activates complement upon binding within the diabetic glomerulus.Methods. We investigated this by comparing complement deposition and activation in kidneys from streptozotocin-induced diabetic mice and healthy control mice.Results. After 20 weeks of diabetes, glomerular deposition of MBL was significantly increased. Diabetic animals had 2.0-fold higher (95% CI 1.6–2.5) immunofluorescence intensity from anti-MBL antibodies compared with controls (P<0.001). Diabetes and control groups did not differ in glomerular immunofluorescence intensity obtained by antibodies against complement factors C4, C3, and C9. However, the circulating complement activation product C3a was increased in diabetes as compared to control mice (P=0.04).Conclusion. 20 weeks of diabetes increased MBL autoreactivity in the kidney and circulating C3a concentration. Together with previous findings, these results indicate direct effects of MBL within the kidney in diabetes.

Reduced Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 is Associated with Disturbed Coagulation in Septic Shock

2019 ◽  
Vol 119 (06) ◽  
pp. 952-961 ◽  
Author(s):  
Julie Brogaard Larsen ◽  
Mathies Appel Laursen ◽  
Christine Lodberg Hvas ◽  
Kim Michael Larsen ◽  
Steffen Thiel ◽  
...  
Keyword(s):  
Septic Shock ◽  
Complement System ◽  
Sofa Score ◽  
Thrombin Generation ◽  
Mannose Binding Lectin ◽  
Lectin Pathway ◽  
Complement Factor ◽  
Mannose Binding ◽  
The Complement System ◽  
Binding Lectin

Background Activation of the complement system is part of the dysregulated immune response in sepsis. The mannose-binding lectin-associated serine proteases (MASP)-1 and -2 activate the lectin pathway of the complement system. Besides, these proteins can activate coagulation in vitro. However, the role of the lectin pathway proteins in the development of sepsis-related disseminated intravascular coagulation (DIC) is only sparsely investigated. Aim This article investigates the association between lectin pathway proteins and coagulation disturbances in septic shock patients. Materials and Methods We included 36 septic shock patients from the intensive care unit, Aarhus University Hospital, Denmark. Blood samples were obtained within 24 hours after admission (day 1), and subsequently on day 2 and day 3. Plasma concentrations of mannose-binding lectin (MBL), H-ficolin, M-ficolin, CL-L1, CL-K1, MASP-1, -2 and -3, MBL-associated proteins of 19 and 44 kDa as well as complement factor C3dg were assessed. Standard coagulation parameters, thrombin generation, thrombin–anti-thrombin (TAT) complex and pro-thrombin fragment 1 + 2 were measured. Sequential Organ Failure Assessment (SOFA) score, DIC score and 30-day mortality were assessed. Results Reduced MASP-1 plasma concentration was associated with DIC score ≥5 (p = 0.02), impaired thrombin generation (p = 0.03) and lower plasma TAT complex levels (p = 0.03). No association was found between lectin pathway proteins and SOFA score or 30-day mortality. Conclusion Reduced MASP-1 concentrations were associated with impaired coagulation in septic shock patients. This indicates that increased MASP-1 activation and consumption is associated with the more severe coagulation disturbances in sepsis and points to a possible role for MASP-1 in sepsis-related DIC.

LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3233-3239 ◽  
Author(s):  
Lijuan Zhao ◽  
Yuko Ohtaki ◽  
Kouji Yamaguchi ◽  
Misao Matsushita ◽  
Teizo Fujita ◽  
...  
Keyword(s):  
Complement System ◽  
Serine Proteases ◽  
Lectin Pathway ◽  
Platelet Response ◽  
O Antigen ◽  
Mannose Binding ◽  
Anaphylactoid Shock ◽  
K 12 ◽  
The Complement System ◽  
Binding Lectin

AbstractIntravenous injection of a lipopolysaccharide (LPS) into mice induces a rapid accumulation of platelets in the lung and liver. When degradation of the accumulated platelets occurs, anaphylactoid shock follows rapidly, the severity of the shock paralleling the quantity of platelets accumulated in the lung. Here we examined the contributions made by LPS structure and the complement system to the platelet response to LPS. BALB/c mice were injected with an LPS fromEscherichia coli O8, O9, O111, or K-12, or from recombinant mutants of K-12. The O-regions of the O8 and O9 LPSs consist of a mannose homopolysaccharide (MHP), while that of O111 consists of a heteropolysaccharide (not including mannose), and K-12 LPS lacks an O-region. O111 LPS was devoid of the ability to induce the platelet response or shock, while the ability of K-12 LPS was weak. The 2 recombinant LPSs—each having an O-region (from O8 or O9) linked to K-12 LPS—exhibited activities similar to or stronger than those of their original LPSs. Mannose-binding lectin (MBL) complexed with MBL-associated serine proteases (MASPs) bound strongly to LPSs containing MHP and caused C4 activation. Moreover, the abilities of these LPSs to activate the complement system corresponded well with their abilities to induce the platelet response and rapid shock. These results suggest that the structure of the O-antigen region is important for the platelet response to LPS, and that activation of the lectin pathway of the complement system is involved in this response.

scholarly journals Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zihao Li ◽  
Mian Wang ◽  
Hua Zhong ◽  
Xin Huang ◽  
Xinyin Wu ◽  
...  
Keyword(s):  
Additive Model ◽  
Lectin Pathway ◽  
Control Group ◽  
Single Nucleotide ◽  
Key Enzyme ◽  
Healthy Control ◽  
Tea Drinking ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Negative Interactions

AbstractMannan-binding lectin-associated serine protease-2 (MASP-2) has been reported to play an important role as a key enzyme in the lectin pathway of the complement system. The objectives of our study were to determine whether the single-nucleotide polymorphism (SNPs) of MASP2 and the gene-tea drinking interaction were associated with the susceptibility to TB. In total, 503 patients and 494 healthy controls were contained. Three SNPs (rs12142107, rs12711521, and rs7548659) were genotyped. The association between the SNPs and susceptibility to TB were investigated by conducting multivariate unconditional logistic regression analysis. The gene-tea drinking interactions were analyzed by the additive model of marginal structural linear odds models. Both genotype AC + AA at rs12711521 of MASP2 genes and genotype GT + GG at rs7548659 of MASP2 genes were more prevalent in the TB patient group than the healthy control group (OR: 1.423 and 1.439, respectively, P < 0.05). In addition, The relative excess risk of interaction (RERI) between tea drinking and rs12142107, rs12711521, and rs7548659 of MASP2 genes was found to suggest negative interactions, which reached − 0.2311 (95% confidence interval (CI): − 0.4736, − 0.0113), − 0.7080 (95% CI − 1.3998, − 0.0163), and − 0.5140 (95% CI − 0.8988, − 0.1291), respectively (P < 0.05). Our finding indicated that the SNPs (rs12711521 and rs7548659) of MASP2 were associated with the susceptibility to TB. Furthermore, there were negative interactions between tea drinking and rs12142107, rs12711521, and rs75548659 of MASP2 gene, respectively. Our research provides a basis for studying the pathogenesis and prevention of tuberculosis.

scholarly journals Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in Oligoarticular and Systemic Juvenile Idiopathic Arthritis

2015 ◽  
Vol 42 (7) ◽  
pp. 1252-1258 ◽  
Author(s):  
Christine Petri ◽  
Steffen Thiel ◽  
Jens Christian Jensenius ◽  
Troels Herlin
Keyword(s):  
Pattern Recognition ◽  
Juvenile Idiopathic Arthritis ◽  
Complement System ◽  
Serine Proteases ◽  
Inflammatory Markers ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Lectin Pathway ◽  
Paired Samples ◽  
Systemic Jia ◽  
The Complement System

Objective.The complement system plays a crucial role in the pathogenesis of inflammatory processes. The lectin pathway of the complement system is activated through the recognition of pathogens by soluble pattern recognition molecules (PRM), i.e., mannan-binding lectin (MBL), collectin-LK, and the ficolins. PRM are reportedly correlated to disease activity in rheumatoid arthritis (RA). The aim was to evaluate the pathogenic role of PRM in juvenile idiopathic arthritis (JIA).Methods.We measured MBL, M-ficolin, H-ficolin, MBL-associated serine proteases (MASP) 1, MASP-2, MASP-3, and 2 alternative splice products, MBL-associated protein (MAp) 44 and MAp19, in plasma and synovial fluid (SF) of children with persistent oligoarticular (n = 109 in plasma, n = 38 in SF) and systemic JIA (n = 19 in plasma, n = 11 in SF). The concentrations of the proteins were measured by in-house time-resolved immunofluorometric assays.Results.We observed significantly higher levels of M-ficolin, MASP-1, MASP-2, and MASP-3 in plasma and SF from patients with systemic JIA compared with persistent oligoarticular JIA (p < 0.001). In paired samples of plasma and SF from 47 patients with oligoarticular and systemic JIA, we observed higher concentrations in plasma for both subtypes for 7 of the measured proteins while the reverse relationship was observed for MASP-3. M-ficolin and MASP-2 correlated to erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and platelet count (p < 0.001). M-ficolin was in addition related to the number of active joints and inversely related to hemoglobin levels.Conclusion.Our results point to plasma M-ficolin and MASP-2 as inflammatory markers in JIA. The levels of all proteins are higher in plasma than in SF, except for MASP-3, indicating that MASP-3 may be produced locally in joints.

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