PNAS: Research reveals the mechanism of systemic allergic reactions.

28, 2020 // In a recent study, researchers at Ludwig-Maximilian University (LMU) in Munich studied how fat cells regulate their calcium levels to control the immune response.immune system protects us from viruses and bacteria, and helps eliminate cancer cells.the innate immune system is responsible for the initial detection and destruction of invasive pathogens., it alerts cells to an adaptive immune system, eliminating infectious organisms and providing long-term protection against them.However, in some cases, the immune response may be misdirected, causing the system to focus its firepower on the wrong target, resulting in autoimmune disease or allergic reactions.now, a team of researchers led by LMU immunopharmacologist Susanna Zierler and pharmacologist found that the activity of certain ion channel proteins in fat cells plays an important role in preventing abnormal and allergic reactions and ensuring that the immune response is not over-regulated.(photo:fat cells are found in almost all organs of the body and regulate the occurrence and retreat of inflammatory responses triggered by the immune system as a means of fighting infections and metabolic abnormalities.immune response is a very complex process that must be carefully targeted.this means that immune cells must be able to detect specific signals that interact with receptor proteins on the cell surface and convert them into well-defined set of molecular interactions, resulting in the activation of the appropriate response at the right time and in the right place.the levels of positively charged ions, including calcium, sodium and potassium, changein in the intracellular response.has proven that rapid and transient changes in ion concentrations are essential for activating multiple types of immune cells.it is clear that cells regulate the intracellular levels of these ions mainly through proteins called ion channels and ion pumps, but it is not clear how these flows are controlled in the event of an immune response.team led by Susanna Zierler and Ingrid Boekhoff studied the function of selectively regulating the ion channels of free calcium concentrations in hypertrophy cells.like many other cell types, fat cells do this by activating the release of calcium from intracellular storage.endoscotopa (ER) is the largest stored organelle of calcium in cells.but other intracellular organelles, such as mitochondria (the power station of cells) and lysosomes (intracellular waste treatment units), can also provide calcium ions on demand.all of these intracellular chambers are defined by the membrane inserted into the special ion channels., for example, the lysozyme membrane contains a protein that belongs to a family known as a two-hole channel (TPC).Zierler, Boekhoff and colleagues report that TPC1 is the main function of regulating changes in the distribution of calcium ions between lysosomes and ER within cells.they demonstrated that selective gene knock-down or pharmacological inhibition of TPC1 in fat cells in mice alters the balance between the amount of calcium stored in these cells.crucially, this change is associated with a significant increase in histamine secretion, which subsequently triggers severe allergic reactions at the cellular and systemic levels. "These results suggest that sensitive regulating balance disturbances that control the levels of calcium ions in the cells in hypertrophy cells can lead to intense allergies and allergic reactions,"Zierler said. the identification of the"TPC1 channel protein as an important regulator of hypertrophy cell activity and histamine secretion" has clear therapeutic significance. "This study suggests that the TPC1 channel is a promising drug target for the treatment of abnormal reactions and hypertrophic cell-dependent diseases," saidZierler.", "In summary, there is great potential for targeted pharmacological control of ion channels in immune cells in the treatment of infections, allergies and even leukemia.() Source: Immune System -- Knocked off Balance Original Source: Elisabeth Arlt, Marco Fraticelli, Volodymyr Tsvilovskyy, Wiebke Nadolni, Andreas Breit, Thomas J. O'Neill, Stefanie Resenberger, Gunther Wennemuth, Christian Wahl-Schott, Martin Biel, Christian Grimm, Marc TPC1 yn y opiaugments athailax and mast cell activity. Proceedings of the National Academy of Sciences, 2020; 201920122 DOI: 10.1073/pnas.1920122117.