LL-37 5mg (CAP-18)

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LL-37 5mg (CAP-18)

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 LL-37 5mg (CAP-18,Cathelicidin) 

 

LL-37: An Antimicrobial Peptide with Immune System Effects

 

LL-37 (a.k.a. CAP-18 or LL37) is a group of peptides known as cathelicidins. Cathelicidin peptides (themselves members of a larger group of proteins called cationic antimicrobial peptides or AMPs for short) are commonly found in the lysosomes of macrophages and other white blood cells. Scientific research has shown they play a critical role in immune defenses against bacteria, fungi, and viruses.

 

LL-37 is the only known human cathelicidin. It is 37 amino acids in length and is an amphipathic (has water-loving and water-avoiding components) alpha helix. It has broad activity against a number of pathogens and is also thought to play a central role in the inflammatory process. Recent research has indicated that LL-37 can activate other immune system components such as mast cells (associated with allergies), monocytes, T lymphocytes, and neutrophils. It also promotes healing and the growth of blood vessels (angiogenesis)1.

 

LL-37 Outperforms Conventional Antibiotics

 

Staphylococcus aureus, staph for short, is one of the largest problems facing modern medicine, particularly since it has become resistant to a number of antibiotics. Research with LL-37 shows that it is effective against staph at nanomolar concentrations, kills the bacteria both when it invades cells and when is free, and is more effective than conventional antibiotics. These features make LL-37 of particular interest to the medical field and it is hoped that the peptide will be useful in treating chronic infections, such as those that afflict individuals with diabetes or immune dysfunction2.

 

What makes LL-37 particularly interesting is that it targets the lipid membrane of bacteria directly, interfering with the structure of the membrane. This is slightly different from how conventional antibiotics work (by interfering with protein components of the membrane). Proteins can easily be altered by mutation, leading to antibiotic resistance. Lipids are not affected by mutations and thus the chances of resistance to LL-37 developing are very small2,3.

 

LL-37 and Tissue Healing

 

The balance between inflammation and tissue healing is a delicate one. Inflammatory responses are absolutely necessary if the body is to fight off invading pathogens. Unfortunately, these same inflammatory responses can prevent adequate healing, promote scar tissue formation, and even lead to autoimmune diseases if left unchecked. LL-37 appears to play a role in balancing inflammation with healing and at least part of that role is mediated through effects on macrophages.

 

Macrophages promote inflammation when foreign pathogens are detected. They do this by first detecting the pathogens and then sending signals to the rest of the body that a defense needs to be mounted. Once the tide shifts and the immune system begins to overtake that pathogens, macrophages begin producing a new set of signals that calm the inflammation so that the body can move to the next phase of healing. It turns out that peptides like LL-37 play an important role in reversing the activation of macrophages4. Simply put, the removal of LL-37 from a tissue causes macrophages to revert to the anti-inflammatory formation. In other words, the presence of LL-37 converts anti-inflammatory macrophages into pro-inflammatory macrophages. Removing LL-37 reverses the conversion and calms the inflammatory response.

 

Resources

1.            Ramos, R., Domingues, L. & Gama, M. LL37, a human antimicrobial peptide with immunomodulatory properties. Available at: http://formatex.info/microbiology3/book/915-925.pdf. (Accessed: 18th February 2017)

2.            Noore, J., Noore, A. & Li, B. Cationic Antimicrobial Peptide LL-37 Is Effective against both Extra- and Intracellular Staphylococcus aureus. Antimicrob. Agents Chemother. 57, 1283–1290 (2013).

3.            Wang, G. Structures of Human Host Defense Cathelicidin LL-37 and Its Smallest Antimicrobial Peptide KR-12 in Lipid Micelles. J. Biol. Chem. 283, 32637–32643 (2008).

4.            Does, A. M. van der et al. LL-37 Directs Macrophage Differentiation toward Macrophages with a Proinflammatory Signature. J. Immunol. 185, 1442–1449 (2010).