Discovery of Neutrophils States May Lead To New Diagnostic Models For Inflammatory Diseases.
Source: Thaialnd Medical News May 31, 2019 5 years, 1 month, 3 weeks, 5 days, 23 hours, 40 minutes ago
Researchers at the University of Toronto have made a discovery about the nature of neutrophils; the most numerous white blood cells in the body, that may lead to new models for diagnosing and tracking inflammatory diseases such as cancer, osteoarthritis and also auto-immune diseases.
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Polymorphonuclear neutrophils (PMNs) are the most abundant leukocytes in the blood and is the first line of host defense against numerous infectious pathogens, such as bacteria, fungi, and protozoa. Neutrophils are the first leukocytes to migrate from the blood to injured or infected sites or organs, for killing pathogens and removing cellular debris. Neutrophils migrate to sites of inflammation and infection where they recognize and phagocytose invading microorganisms, in order to kill them via different cytotoxic mechanisms.
Billions of neutrophils are made in the bone's marrow each day to protect the body and attack microbial invaders.
"In the past, it was assumed that there is one type of neutrophil in circulation in health individuals," says Michael Glogauer, Professor at the Faculty of Dentistry and acting chief dentist at the Princess Margaret Cancer Centre in a telephone interview with Thailand Medical News.
"We however discovered two distinct neutrophil states in blood, and these amounts vary depending on the health of patient and if there are prevailing acute or chronic infections," added Glogauer, who is one of the authors of the study.
The research team discovered this unique subset of immune cells after developing a new method of preserving and analyzing neutrophils in blood, overcoming a longstanding difficulty in how to study these short-lived and easily activated immune cells.
One group of neutrophils called the primed neutrophils, or pPMNs,were discovered to be in a state of constant readiness to fight infections, comprising up to 10 per cent of the overall population of neutrophils. These were seen to be in contrast to the more available "resting state" neutrophils (rsPMNs), which circulate the blood in a naive state.
The research team then tested blood samples from animal models with acute infections and also humans with chronic gingivitis, tracking both the prime and resting neutrophils. It was seen that when an acute infection flares up, the primed warrior cells quickly leave the blood stream and enter the tissues.
In both animal and human models with acute inflammation, the primed cells disappear from the bloodstream rapidly and enter inflamed tissues within 15 minutes. Within one to three hours, the remaining resting state neutrophils also become activated, and follow the initial group into the tissues or organs.
The discovery may help in disease detection and monitoring. If the percentage of primed neutrophils in the blood is constant in a healthy state, hovering at around 10 per cent, then it follows that one could can track the state of the activation of the innate immune system where the expectation would be elevated levels of this primed population.
Blood samples from those who are experiencing inflammatory disease attacks, for instance, can be looked at for the number of primed neutrophils as an indicator of the activation state of the immune system, indicating to doctors exactly how acute a
n infection is across a wide range of inflammatory diseases such as cancer, arthritis ,diabetes and even certain auto-immune diseases.
The research team is currently testing neutrophil populations both just before and after cardiovascular surgery, as well as patients with rheumatoid arthritis and periodontitis.
The discovery may also lead to new standards for health research.
Reference: Noah Fine et al, Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation,
Blood Advances (2019).
DOI: 10.1182/bloodadvances.2018030585
