I've just concluded my first week as an intern at Massachusetts General Hospital’s Center for Engineering in Medicine and Surgery (CEMS). I will be spending ten weeks at Shriners Children’s Hospital in Boston as an intern under an assigned postdoctoral researcher. My research centers around studying potential future therapeutics for sepsis, which is the body’s extreme, unbalanced response to infection. During septic shock, the immune system is unable to maintain homeostasis, and its innate defense mechanisms cause hyperinflammation and immune suppression. Emerging laboratory research suggests, however, that specific anti-inflammatory lipid mediators called resolvins are able to reduce the body’s overreaction to infection.
To measure the effect of resolvin, we are studying two types of immune cells– monocytes and neutrophils. Neutrophils are the body’s first line of defense and are the most common immune cell, making up about 60% of immune cells. While monocytes are the rarest white blood cells and only make up 2%-8% of WBCs, their width (known as monocyte distribution width, or MDW) is a reliable, recently FDA-approved marker of septic progression. In the lab, we use MDW to check whether patient blood is healthy or diseased before performing further analysis.
After isolating the monocytes, we then divide the cells into wells on a plate and assign each well a different treatment (including untreated control samples, samples with bacteria, and samples with bacteria and varying concentrations of resolvin). Immune cells release cytokines, substances such as interferons, interleukins, and growth factors that help activate other parts of the immune system. The body has 13 inflammatory cytokines, and to measure the presence of each of these cytokines, I analyze our monocyte samples with an assay known as LEGENDPlex. We then compare the results for each treatment in order to determine the effect of resolvin on the levels of inflammatory cytokines released. We also monitor MDW, since change in monocyte size indicates that the cells are making new proteins associated with cytokine release.
Neutrophil analysis is another key component of analyzing the effect of resolvin on the immune system. While neutrophils are critical for immune response, they also contribute to the development of numerous inflammatory conditions; learning how to manipulate neutrophil function could benefit patients experiencing infection or inflammation. In order to control the spread of infection, neutrophils perform ‘swarming,’ a process by which they cooperate to send signals and gather around pathogens, restricting potential growth. MGH has pioneered novel assays that allow researchers to study neutrophil swarming, and so we use this cutting-edge technique to visualize the swarming patterns of neutrophils after being treated with resolvin.
In addition to this fascinating immune research, we are working on a side project studying a little-understood ability of mitochondria, organelles which fuel cellular respiration. MGH research has shown that fresh mitochondria can revive dying cells; in animal studies, mitochondrial transplants revived heart muscles stunned from a heart attack, along with injured lungs and kidneys. This research represents a promising new hope for transplantation– mitochondria infusions could extend the limited window of organ viability, which limits the long-distance transportation of organs and further contributes to the organ shortage.
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