Histidine-rich glycoprotein (HRG) linked to sepsis prevention

Emobileclinic Researchers Corner



Researchers at Okayama University, Shujitsu University and Kinki University, al in Japan have found Histidine-rich glycoprotein (HRG), a naturally occurring protein useful in the prevention of Sepsis. This finding was published in the eBioMedicine Journal.

Sepsis is blood poisoning following an infection or injury is known as sepsis, and is a major cause of death across the world. Sepsis occurs when the body’s immune system goes into overdrive, resulting in damage to its own tissues and organs through insufficient blood supply. However, the exact molecular mechanisms underpinning sepsis and its progression are unclear.

It is against this background that Professor Masahiro Nishibori and co-workers at the three Japanese Universities embarked on this study. They found that HRG controls the shape and activity of white blood cells called neutrophils, enabling them to flow freely and respond correctly in the fight against sepsis.
The team aimed to verify the role of HRG – a protein produced and secreted by the liver because HRG levels decrease rapidly in patients when sepsis takes hold. HRG is known to be involved in the regulation of immune responses, as well as prompting antibacterial and antifungal activity. The team induced sepsis in one group of mice, keeping a healthy group as controls. They purified HRG from human blood plasma, and treated some of the septic mice with a dose of the protein.

The researchers discovered that the HRG mice quickly regained locomotor activity, and began to recover from sepsis. Further investigations showed that the mice exhibited far less inflammation in the lungs than their non-treated counterparts. Neutrophils in the HRG mice were smooth and spherical in shape, allowing them to flow freely through microcapillaries and veins.
The septic mice, however, had deformed neutrophils with irregular shapes. This in turn triggered unwanted activity because the deformed neutrophils became attached to other cells, creating cell clusters that limited blood flow.
Sepsis is caused by the body’s own response to an infection or an infected injury. Essentially, the immune system goes into overdrive and ends up damaging major organs and tissues by limiting the blood supply. Scientists theorised that sepsis must have its origins in the disruption of healthy cells in the blood, but the precise mechanisms are not yet clear.

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The work by Nishibori and his team clarifies the role of histidine-rich glycoprotein (HRG) in tackling sepsis. While it is not yet clear why HRG expression falls as sepsis sets in, this study shows that the loss of HRG in blood plasma is a key factor in sepsis. The decrease in HRG appears to trigger abnormal, deformed white blood cells(neutrophils), which clump together with other cells in the vasculature system and limit blood flow.
In this study, mice given a boost of human HRG during sepsis began to show rapid signs of improvement and increased chances of survival. The neutrophils in the treated mice regained the smooth and spherical shape needed to pass freely through capillaries and the veins, and the blood supply was reinstated.

Source eBioMedicine Journal (August 2016)

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