Construction of a tissue-specific protein abundance atlas. (a) Vascularized organs, plasma and cells adjacent to the blood plasma were collected from healthy Balb-C mice. The collected organs and cells were washed in PBS, homogenized, the proteins digested with trypsin and analysed by shotgun LC-MS/MS. (b) The scaled spectral counts from the LC-MS/MS analysis of the individual organs and cells were correlated using Pearson’s r correlation coefficient, indicated by the numbers in the heat map. (c) Heat map of the scaled spectral counts of the different cell and organs. The grey lines in the heat map shows percentage of signal associated with a given organ or cell type. Total number of identified proteins per organ, blood vessel and cells is shown in brackets below the heat map.
Research groups in Lund and Zurich have now developed a way to use mass spectrometry to measure hundreds of proteins in a single blood sample. With the help of protein patterns it is then possible to determine the severity of the condition and which organs have been damaged. “We use the blood as a mirror reflecting what happens in the body,” says Johan Malmström. The team has been able to map the majority of all proteins that can be found in vital organs such as the heart, lung, liver, spleen and blood vessels, and listed which proteins are specific to each specific organ.
“If you see in a blood sample that the amount of proteins from a specific organ increases, it indicates damage to this organ. The method provides an understanding of the molecular events that take place during the course of a disease, and the possibility, using the same analysis, to study how different organs are affected,” explains Erik Malmström.
Sepsis (formerly called blood poisoning) is caused by a bacterial infection, and is a condition in which the immune system starts to react erroneously in different ways. However, it is often difficult to diagnose, because the symptoms of sepsis – including high breathing rate, fever, rapid pulse, pain and confusion – occur in milder conditions as well. Also, the progression of the disease can be very fast, and become fatal in just a few hours. Therefore, there is a great need for faster diagnosis and better understanding of the course of the disease.
Another researcher at Lund University, Adam Linder, has begun to develop a diagnostic method based on the protein HBP. This protein is emitted from the white blood cells and reflects the risk of hypotension.
The Malmström group’s study of hundreds of different proteins could eventually be used to select other important proteins that can serve as biomarkers for different aspects of sepsis. First and foremost, however, the method is an important research tool.
“There is so much we don’t know about sepsis. Why do not all patients react the same way – why do some organs suffer the most damage in some patients and not in others? Do different bacteria cause the disease to progress? Can you divide patients into different subgroups, or bacteria, or does each new combination of patients and bacteria lead to a specific form of sepsis?” asks Erik Malmström.
The researchers have conducted their studies on animals, but are now moving on to human tissue. Through a collaboration with surgeons at Skåne University Hospital they have obtained samples of healthy tissue from all organs concerned. Protein patterns of these samples can then be compared with the corresponding tissue in sepsis patients.
“Protein mapping like this has never been done before. The method can also be applied to other diseases for studying how pathological changes in various organs are reflected in a blood sample,” says Johan Malmström. http://www.alphagalileo.org/ViewItem.aspx?ItemId=159972&CultureCode=en
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