Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo

Immunobiology ◽  
2006 ◽  
Vol 211 (10) ◽  
pp. 759-766 ◽  
Author(s):  
Meghan E. McMullen ◽  
Melanie L. Hart ◽  
Mary C. Walsh ◽  
Jon Buras ◽  
Kazue Takahashi ◽  
...  
Keyword(s):  
Mannose Binding Lectin ◽  
Complement Pathway ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Mannose binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Meghan E McMullen ◽  
Melanie L. Hart ◽  
Mary C. Walsh ◽  
Jon Buras ◽  
Kazue Takahashi ◽  
...  
Keyword(s):  
Mannose Binding Lectin ◽  
Complement Pathway ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Mannose-binding Lectin-deficient Mice Are Susceptible to Infection with Staphylococcus aureus

2004 ◽  
Vol 199 (10) ◽  
pp. 1379-1390 ◽  
Author(s):  
Lei Shi ◽  
Kazue Takahashi ◽  
Joseph Dundee ◽  
Sarit Shahroor-Karni ◽  
Steffen Thiel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Susceptibility Gene ◽  
Humoral Response ◽  
Mannose Binding Lectin ◽  
Host Responses ◽  
Mannose Binding ◽  
Disease Susceptibility Gene ◽  
Binding Lectin

Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Humoral response molecules together with phagocytes play a role in host responses to S. aureus. The mannose-binding lectin (MBL, also known as mannose-binding protein) is an oligomeric serum molecule that recognizes carbohydrates decorating a broad range of infectious agents including S. aureus. Circumstantial evidence in vitro and in vivo suggests that MBL plays a key role in first line host defense. We tested this contention directly in vivo by generating mice that were devoid of all MBL activity. We found that 100% of MBL-null mice died 48 h after exposure to an intravenous inoculation of S. aureus compared with 45% mortality in wild-type mice. Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus. Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and raises the idea that the MBL gene may act as a disease susceptibility gene against staphylococci infections in humans.

scholarly journals Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood in vitro

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 616 ◽  
Author(s):  
Annette Scheid ◽  
Ning Li ◽  
Carleen Jeffers ◽  
Francesco Borriello ◽  
Sweta Joshi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Peptide ◽  
Cord Blood ◽  
Mannose Binding Lectin ◽  
Human Cord Blood ◽  
Mannose Binding ◽  
Binding Lectin

Background: There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. Methods: The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12–14) against Staphylococcus aureus (SA) USA 300 (2x104 CFU/ml), Staphylococcus epidermis (SE) 1457 (2x104 CFU/ml) and Candida albicans (CA) SC5314 (1x104 CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. Results: Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested in vitro. rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. Conclusions: To the extent that our in vitro results predict the effects of APPs in vivo, development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen.

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 Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

2005 ◽  
Vol 191 (10) ◽  
pp. 1697-1704 ◽  
Author(s):  
W. K. Eddie Ip ◽  
Kwok Hung Chan ◽  
Helen K. W. Law ◽  
Gloria H. W. Tso ◽  
Eric K. P. Kong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Serum Levels ◽  
Mannose Binding Lectin ◽  
In Vitro Assays ◽  
Calcium Dependent ◽  
Control Subjects ◽  
Mannose Binding ◽  
Carbohydrate Recognition Domains ◽  
Binding Lectin

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS

scholarly journals Origin of Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 and MASP-3 Involved in the Lectin Complement Pathway Traced Back to the Invertebrate, Amphioxus

2003 ◽  
Vol 170 (9) ◽  
pp. 4701-4707 ◽  
Author(s):  
Yuichi Endo ◽  
Masaru Nonaka ◽  
Hidetoshi Saiga ◽  
Yuji Kakinuma ◽  
Akiko Matsushita ◽  
...  
Keyword(s):  
Serine Protease ◽  
Mannose Binding Lectin ◽  
Complement Pathway ◽  
Mannose Binding ◽  
Binding Lectin
Sign in / Sign up

Export Citation Format

Share Document