Is Mannose Binding Lectin a TNF-α inhibitor? 2022 study

[pattismith]

Like many CFS patients, I have MBL deficiency (undetectatble in my serum), so this paper caught my eyes.

It suggests that under some circumstances, MBL can stop TNF-α action.

A previous study in 2001 found the same anti-inflammatory effect of MBL.



Mannan-Binding Lectin Deficiency Limits Inflammation-induced Myeloid-Derived Suppressor Cells Expansion via Modulating Tumor Necrosis Factor Alpha-triggered Apoptosis (ijbs.com)

Mannose-Binding Lectin Regulates the Inflammatory Response of Human Professional Phagocytes to Neisseria meningitidis Serogroup B | The Journal of Infectious Diseases | Oxford Academic

 

[Learner1]

@pattismith Interesting topic. Did you mean to have leptin in the title and not lectin?

My MBL is high. Not sure what it means, though....

 

[pattismith]

@pattismith Interesting topic. Did you mean to have leptin in the title and not lectin?

My MBL is high. Not sure what it means, though....

It was already observed that if you want to live a long life, you'd better have a moderate amount of MBL, it means not too much or not too few of it...

If you have moderate MBL blood level, it has some antiinflammatory effect.

In this 2019 study, it was shown that MBL can bind some cells and downregulate COX2.

This means that MBL deficiency will increase inflammation in these cells compare to someone with a moderate amount of MBL.

The study shows that MBL bind to calreticulin on the cell surface. Endothelium cell have the calreticulin on their surface, so MBL may have antiinflammatory effect on the endothelium

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343806/#CIT0012

 

[pattismith]

a new article pointing anti TNF alpha activity of MBL​

Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury​

Abstract​

Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE−/− mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed.

Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury.
MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels.

Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding.

https://www.mdpi.com/2227-9059/11/6/1743

 

[datadragon]

the NLRP3 inflammasome links complement-mediated inflammation and IL-1β release as complement subsequently elicits secretion of both IL-1β and IL-18 in vitro and in vivo via the NLRP3 inflammasome. https://pubmed.ncbi.nlm.nih.gov/23817414/

The addition of high concentrations of MBL (>6 μg/mL) profoundly decreased the production of interleukin (IL)–6, IL-1β, and tumor necrosis factor–α by monocytes in response to meningococci, whereas lower concentrations enhanced the production of IL-6 and IL-1β. These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease. In an ex vivo model, the addition of MBL to the blood of MBL-deficient donors influenced the production of monocyte-derived inflammatory cytokines.

So thats an interesting add that in some cases it can also regulate inflammation, but generally the focus I believe should remain on NLRP3 which would block any subsequent inflammatory event and its downstream effects. Keep in mind of course that NLRP3 is needed for a proper TH1 response and so you only want to do this when its chronically high.

My MBL is high. Not sure what it means, though....

That would suggest either added inflammation or possibly helping with a overactive immune response and would have to check high sensitivity c-reactive protein and other inflammatory markers to see.

-David

 

[pattismith]

MBL deficiency has a proinflammatory phenotype, it can explain it's assocition with many inflammatory diseases​

​

Is mannose binding lectin deficiency a prerequisite for the development of guttate psoriasis? 2014​

Background:
Psoriasis is a T cell-mediated immune disease in which various cytokines, primarily tumor necrosis factor-α (TNF-α), are complexly involved.

Mannose-binding lectin (MBL) gene polymorphisms decrease MBL serum levels, thereby increasing the synthesis of proinflammatory cytokines such as TNF-α.

Objectives: This trial was designed to evaluate the role of the MBL2 codon 54 polymorphism in the pathogenesis of psoriasis.

Methods: Fifty patients diagnosed with psoriasis vulgaris and 53 healthy subjects were included in the trial.

Results: A total of 33 (66.0%) of the 50 psoriasis patients were detected to have A/A genotype and 17 (34.0%) had B/B genotype.
Of the control subjects, 44 (83.0%) had A/A genotype and nine (17.0%) had B/B genotype.

There was a statistically significant difference between the groups (P = 0.047).

The analysis of allele frequencies revealed A allele prevalences to be 79 (79.0%) and 95 (89.6%), and B allele prevalences to be 21 (21.0%) and 11 (10.4%), in the patient and control groups, respectively. A statistically significant difference between allele frequencies was detected (P = 0.031).

Conclusions: This study suggests that the MBL2 codon 54 polymorphism may have an association with psoriasis in the Turkish population.