Malfunction of molecular signaling system removes mature blood cells fighting against sepsis -
When the body encounters an infection, molecular signaling system ramps up system infection battle of the body to produce more white blood cells to attack invading bacteria. Now researchers have discovered that face a massive bacterial infection leading to sepsis, the same failure of the signaling system, damaging the body's ability to fight the invaders.
In addition to the removal of mature blood cells fighting against the infection, dysfunction of this signaling system causes permanent damage to the blood producing cells in the body - called hematopoietic stem cells - which are found in the marrow bone. The research, by scientists at the Medical School of the University of Indiana, was recently published in the journal Stem Cell Reports . http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(16)30057-1
Sepsis is a life threatening inflammatory response by the body system which can lead to serious bacterial infections. It is a growing problem: The number of hospitalizations for sepsis more than doubled from 00 to 08, reaching more than 1.1 million, according to the Centers for Disease Control and Prevention. Patients with severe sepsis or septic shock has a death rate (deaths) of about 40% -60%, with seniors with the highest mortality rates. Newborns and pediatric patients with sepsis have a mortality rate of 9% -36%.
"Our goal is to know what are the causes of this failure of the bone marrow during severe infections, and find ways to prevent," said Nadia Carlesso, MD, Ph.D., professor of pediatrics and of medical and molecular genetics at the IU school of medicine.
most research has focused on understanding and managing the late consequences of sepsis while little is known about the changes that occur in the bone marrow at early stages of the response to bacterial infection, when the opportunity for effective treatment could be available. The group of Dr. Carlesso has pioneered the study of bone marrow responses during acute infection. laboratory models with severe sepsis his group discovered that producing blood stem cells fail to continuously generate mature neutrophils, which are fighting the most critical cell bacteria.
"In this research, we determined that in cases of severe infection and sepsis, a key mechanism in the response of the body to infection is broken. These results indicate potential new targets for immune protection during major infections, "said Dr. Carlesso.
IU researchers focused on a set of proteins called toll-like receptors, which function as sentinel on cell surfaces. When the receivers detect the presence of invading bacteria, they send signals to the body's immune response system. researchers IU looked receptors toll 4 (TLR4), which activates both signaling pathways that stimulate producing more neutrophils in their current infections but eliminate during severe infections.
in a laboratory sepsis model using mice, the researchers found that two abnormal effects activated receptors toll 4 during a serious infection - removal of neutrophil production and damage-producing stem cells from bone marrow blood -. are mediated by two different molecules downstream of TLR4
"this study is a good start, which provides a more precise map to follow, but more research is needed to better understand this process and develop better, necessary, treatment strategies for many sepsis, "said Dr. Carlesso.
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