Kan viden om hajer hjælpe med at forklare ME- og EHS-sygdomsmekanismen?

Der må findes en biologisk forklaring på, hvorfor nogle ME patienter udvikler elektromagnetisk hypersensitivitet (EHS) mod selv ekstremt lave felter. Måske kan viden om hajer hjælpe os på sporet.

Hajer er de mest "el-følsomme" dyr i verden. De kan mærke felter med så lav en værdi som 5 nV/cm. Det elektriske felt bliver opfanget af sensorer, der kaldes ampullae of Lorenzini. Hajerne anvender deres sensorer til at mærke de svage elektriske felter fra deres byttedyr. Det er observeret, at hajer kan gå til angreb på telegraf-kabler på havets bund, fordi de fejlagtigt opfattes som byttedyr (1, 2).

Ampullae of Lorenzini indeholder keratansulfat, som er en proton (H+) conductor (en elektrisk leder). Det betyder, at protonerne (H+) kan blive transporteret langs med keratansulfat molekylekæder, som er omgivet af vand (H2O). H+ vandrer langs rækken af hydrogenbindinger mellem (H2O og hydrofile enheder (se figur 1 i reference 3). Hver ampul indeholder et lag af celler, der kan opfange de elektriske signaler. Mellem cellerne er der tætte samlinger, således at der ikke kan forekomme lækstrøm mellem cellerne (2, 3).

Fig 1 from reference 3. The keratan sulfate.

(A) Chemical structure of KS. (B) An illustration of a three-monomer segment of KS. Possible intra- and inter-molecular hydrogen bonds as well as the hydrogen bonds between the water of hydration and the polar parts of the molecule form a continuous network comprised by hydrogen-bond chains. The sulfate group interacts with the hydrogen-bond network and forms an H3O+ (hydronium) ion. https://doi.org/10.1371/journal.pone.0202713.g001

Protonerne (H+) i vandige opløsninger bindes til H2O og eksisterer således som H3O+. Protonerne (H+) eksisterer kun under 1% af tiden, hvor de overføres fra et vandmolekyle til et andet. En grundig beskrivelse af fænomenet findes i DeCourseys review, reference 4.


Bemærk at artiklen om keratansultat i hajer hedder (3):
Proton conductivity of glycosaminoglycans

Glycosaminglycaner  (GAGs) er lange kæder af polysakkarider.  Der findes fem typer GAGs (5):

• heparan sulfate
• chondroitin sulphate
• dermatan sulphate
• keratan sulphate
• hyaluronic acid

Dvs der er flere typer GAGs med proton conductivity (kan lede protoner). Herudover kan også kollagen være leder for protoner (3).

Vores extracellulære matrix (ECM) er fyldt med GAGs. 

Mellem alveolar epithelium og kapillær endothelium findes et tyndt lag ECM med GAGs og kollagen (5). På jævnt dansk: I et tyndt lag mellem det fine lungevæv og de små fine blodkar findes ECM (figur 2 i reference 5).

Dette lag har stor betydning for udveksling af ilt, kuldioxid og protoner (figur 24 i reference 4, 5). Og det har betydning for immunforsvar, lungesygdomme og astma (5).

Et nærliggende spørgsmål er om det også kan have betydning for iltoptagelse ved motion? Eller betydning for multiple chemical sensitivity (MCS)?

Og kan en dysregulering af GAGs og/eller lækstrøm i utætheder forårsage EHS?


YOU TUBE:

INTERVIEW EXTRA: Ampullae of Lorenzini

https://www.youtube.com/watch?v=0QVE1dFXFRo

How Do Sharks and Rays Use Electricity to Find Hidden Prey?

https://www.youtube.com/watch?v=JDPFR6n8tAQ

Referencer:
1) Electroreception https://en.wikipedia.org/wiki/Electroreception

2) Ampullae of Lorenzini
https://en.wikipedia.org/wiki/Ampullae_of_Lorenzini


3) Selberg, Manping, Rolandi (2019): Proton conductivity of glycosaminoglycans. Plos One Published: March 8, 2019
https://doi.org/10.1371/journal.pone.0202713

4) DeCoursey TE. Voltage-gated proton channels and other proton transfer pathways (vol 83, pg 475, 2003). Physiological Reviews. 2003 Jul;83(3):1067–.
https://www.physiology.org/doi/full/10.1152/physrev.00028.2002

5) Souza-Fernandes AB1, Pelosi P, Rocco PR
Bench-to-bedside review: the role of glycosaminoglycans in respiratory disease. Crit Care. 2006;10(6):237.
https://www.ncbi.nlm.nih.gov/pubmed/17118216

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Photoimmunology and the ME IDO metabolic trap

The sun emits ultraviolet radiation (UVR) with different wavelengths:

• UVA (320 - 400 nm)
• UVB (280 - 320 nm)
• UVC (< 280 nm)

UVR can cause sunburn and increase the risk of skin cancer. UVR is also immunomodulatory and can be beneficial in the case of inflammatory and autoimmune diseases, but UVR can also exacerbate some autoimmune diseases (1, 2).

Chromophores are the parts of a photorecpetor that absorb photons in light (1).

UVB radiation can be absorped by cytosolic tryptophan, which thus function as a chromophore. This results in the formation of tryptophan photoproducts in particular 6-formylindolo[3,2-b]carbazole (FICZ). FICZ binds to aryl hydrocarbon receptor (AhR) and activates downstream signalling pathways, which contribute to UVR-induced immunosupression (1).


Figur 1 from reference 3. Light dependent synthesis of FICZ. 6-Formylindolo[3,2-b]carbazole (FICZ) is formed by the action of light on tryptophan. FICZ activation of AhR regulates important biological pathways and increases expression of CYP1A1 as a feedback mechanism to induce its own metabolism (3).

AhR activation by FICZ reduces receptor for IgE (FcεRI) and upregulates IDO expression in Langerhans cells (4).

The IDO metabolic trap hypothesis for ME suggests that antigen-presenting cells are driven into a pathological state with increased cytosolic tryptophan. The following decrease in kynurenine products (including FICZ) may disturb the immune system homeostasis (5).

Several ME patients get better in the sun. Is it because sun-induced FICZ moderate the immune system?

References: 
1) Bernard, J.J., Gallo, R.L. & Krutmann, J. Photoimmunology: how ultraviolet radiation affects the immune system. Nat Rev Immunol 19, 688–701 (2019) doi:10.1038/s41577-019-0185-9

https://www.nature.com/articles/s41577-019-0185-9

2) Fritsche et al: Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc Natl Acad Sci U S A. 2007 May 22;104(21):8851-6. Epub 2007 May 14. https://www.ncbi.nlm.nih.gov/pubmed/17502624

3) Zhang, C., Creech, K.L., Zuercher, W.J. et al. Gram-scale synthesis of FICZ, a photoreactive endogenous ligand of the aryl hydrocarbon receptor. Sci Rep 9, 9982 (2019) doi:10.1038/s41598-019-46374-7 
 https://www.nature.com/articles/s41598-019-46374-7

4) Koch et al: AhR mediates an anti-inflammatory feedback mechanism in human Langerhans cells involving FcεRI and IDO. Allergy. 2017 Nov;72(11):1686-1693. doi: 10.1111/all.13170. Epub 2017 May 10. https://www.ncbi.nlm.nih.gov/pubmed/28376268

5) Efimov et el. The mechanism of substrate inhibition in human indoleamine 2,3 dioxygenase. J Am Chem Soc. 2012 Feb 15;134(6):3034-41. doi: 10.1021/ja208694g. Epub 2012 Feb 2. https://www.ncbi.nlm.nih.gov/pubmed/22299628