Calcium as inflammatory stimulus
That the body is important for numerous processes calcium becomes an inflammatory stimulus when it accumulates amplified in the space around the cells. This extracellular calcium activates the so-called inflammasome, a large protein complex, which is a crucial part of the immune system because it controls inflammation. The Leipzig group led by Prof. Ulf Wagner and Dr. Manuela Rossol, rheumatologist at the University of Leipzig, could now describe the upper end of the molecular pathway that calcium turns the mechanism: The Entzündungsweg is via two receptors triggered detect calcium.
receptor GPRC6A
One is the long-known classical calcium receptor, which belongs in the parathyroid. There, the calcium level is measured and controlled. Even with a slight deviation of the calcium levels may cause problems and systemic effects on the organism. As a result, it regulates against immediately, so it is hardly possible to intervene therapeutically in this sensitive system location.
The second (G-protein coupled) receptor with scientific name "GPRC6A" is a recent discovery in the context of inflammation. It does not exist in every cell, but in any case on the circulating blood phagocytes (monocytes). After the researchers considered this receptor is likely in a local inflammatory response is important, so it can be inhibited without bringing equal to total systemic calcium metabolism confusion. This therapeutic approaches open up, says Ulf Wagner: "Our medium-term goal is to seek, together with our pharmacologist, Professor Michael Schaefer, inhibitors of this receptor and to develop."
Important protective reaction with certain "side effects"
An inflammation, also called inflammation is in the body basically an important process to ward off infection, which should not be inhibited as possible. But almost all the common diseases such as diabetes and rheumatism and vascular or tumoral diseases and even obesity and degenerative brain diseases are associated with inflammation. "In rheumatology and internal medicine, we often have to deal with acute infections," said Wagner, "but with long-term chronic disease and the inflammation is almost always bad.
Therefore we want to suppress them therapeutically. "
As a result of chronic inflammation, it always comes to calcium deposits, for example, in vessels or in adipose tissue, which are clearly visible on radiographic images. The researchers knew that the free calcium levels had to have played a role in the process at some point, but the reason was unknown. "We have found the very strong freight free soluble, biologically active calcium ions, so no fancy calcium crystals, inflammation", Ulf Wagner explains the research approach. "We have studied in various tissues. Extracellular calcium stimulates the cells. This was not previously known and is an entirely new finding."
In cells calcium is stored at a high concentration. Her death, ie the death of tissue, it releases an increased extent and so fired the ignition. Decisive here is the concentration in the whole blood, but the local concentration in the tissue. It increases whenever precipitate calcium crystals. The radiograph visible calcifications are precipitated crystals. They are an expression of the fact that at this point the calcium ion concentration was increased, and there has been inflammation. "The mechanism we have described can bring increased calcium values with the degree of inflammation in combination," said Wagner, "and describes an all Subjects Affected, a general principle."
Background knowledge
In the human body calcium plays an important role and is quantitatively the most abundant mineral. The majority is in teeth and bones. The latter serve as memory, can be released from the case of a deficiency state as needed calcium. In the cells of the chemical element is involved in many processes, for example in cell division. It may also muscles and nerves excite and activate enzymes and hormones. Outside the cells, it is involved among others in blood clotting and maintains the cell membrane stable. Calcium is regularly taken in with food.
Prof. Christoph Baerwald, head of rheumatology at the University Hospital Leipzig, provides calcium pills and supplements by now critical. "Especially in rheumatology has prescribed in the past, many patients extra calcium to stop bone changes. Meanwhile, two large studies have shown that even a slightly elevated levels can initiate cardiovascular changes. Therefore, one should be careful with uncontrolled intake. A additional revenue should only be done if you have previously determined the mirror. if the is increased normal or slightly, you should not take additional, otherwise messed up the recording process, which can lead to kidney stones or pseudogout, "said the expert.
Einschätzend on the present basic research in his team says Christoph Baerwald: "It is a completely new perspective that can stimulate an inflammatory reaction with calcium and therefore have to look at all such reactions by the calcium The other aspect that one via G protein. -coupled receptors can inhibit inflammation and thus is a pharmaceutical intervention option, also is a completely new field and could represent a major breakthrough. " work more Leipziger research groups on this topic.
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http://www.nature.com/ncomms/journal/v3/n12/full/ncomms2339.html Specialist publication in nature communications, doi: 10.1038 / ncomms2339
Source: Leipzig [Uni]
