Endotoxin originates from the outer membrane of gram-negative bacteria. Therefore, it is abundant in our environment and can easily contaminate laboratory equipment and reagents. When endotoxin is present in vaccines and other injectable drugs, pyrogenic reactions can occur, ranging from fever and chills to fatal septic shock. For this reason, peptides&elephants controls its peptide syntheses and ensures that its peptides are free of endotoxins.
Endotoxins are lipopolysaccharides (LPS) or, more narrowly, lipid A molecules – the toxic components of lipopolysaccharides. When gram-negative bacteria die, large amounts of endotoxin are released from their outer membrane. Living gram-negative bacteria can also shed endotoxin: When growing, the bacteria split off endotoxin-containing vesicles, which are used for chemical communication and can contain DNA, signaling molecules or defense enzymes.
Since endotoxins are extremely heat-stable, normal sterilization cannot destroy them. Due to their hydrophobic content, they also adhere well to hydrophobic materials such as laboratory beakers, stirring rods and other plastic lab utensils. Endotoxin contamination can therefore spread easily.
Endotoxin sets off inflammatory cascades
Endotoxin reacts with receptors on immune cells and can cause severe symptoms, if it enters the body. For example, endotoxin can bind to CD 14 in the membrane of macrophages, whereupon they secrete inflammatory mediators such as IL-1, IL-6, IL-12 and TNF-α. The macrophages also respond by releasing CD 14 into the environment. [1] When CD 14 binds to endothelial cells, the cells express more selectins and integrins. As a result, leukocytes and thrombocytes increasingly adhere to the vessel walls and activate blood clotting and the release of kinins. Thrombi form and disrupt microcirculation, while the released kinins cause vasodilation. Impaired microcirculation and shock due to vasodilatation can lead to organ failure.
In addition, high concentrations of endotoxin can significantly influence the metabolic activity of cancer cells. [2] Endotoxin can trigger their proliferation and invasion and drastically alter the effectiveness of novel macrophage-modulating immunotherapies.
Endotoxin-free peptides guaranteed
Therefore, peptides&elephants has carefully designed its manufacturing processes to prevent endotoxin contamination. In 2016 peptides&elephants initiated a testing program where samples are taken and analyzed for endotoxins and sterility. The analysis is carried out by the independent BMA laboratory in Germany, which is accredited according to DIN EN ISO/IEC 17025:2018. Their results regularly show: All tested peptides and peptide pools are endotoxin-free and sterile.
Literature ___________________________________________________________________
[1] Sharygin D, Koniaris LG, Wells C, Zimmers TA, Hamidi T. Role of CD14 in human disease. Immunology. 2023 Jul;169(3):260-270. doi: 10.1111/imm.13634.
[2] Heinrich MA, Heinrich L, Ankone MJK, Vergauwen B, Prakash J. Endotoxin contamination alters macrophage-cancer cell interaction and therapeutic efficacy in pre-clinical 3D in vitro models. Biomater Adv. 2023 Jan;144:213220. doi: 10.1016/j.bioadv.2022.213220.