Nat Immunol: Study explains molecular markers of fatal sepsis

January 5, 2021 // -- A glycolycolytic protein may exacerbate inflammation and sepsis, which kills more than 270,000 people a year in the United States alone, researchers at UConn Health reported in the January 4 issue of Nature Immunology.
is mainly caused by bacterial infections.
the immune system out of control and triggers cytokine storms, in which case proteins that cause inflammation flood into the bloodstream.
organs can rupture and death often follows.
(Photo: www.pixabay.com) other diseases can also cause cytokine storms.
medical historians believe that cytokine storms were behind the 1918-1919 flu epidemic and the "black death" death rate.
cytokine storms were also observed in patients with severe COVID-19 and were associated with COVID-19 deaths.
cause of cytokine storms during sepsis is the body's overreaction when an intracellular infection is detected.
When a cell detects a fragment of bacteria or bacteria inside itself, it activates a protein that punctures holes in the cell membrane from the inside, eventually causing the cell to suddenly rupture and spill cytokines into the bloodstream.
cytokines are warning signals that evoke the immune system against bacteria.
also make other cells more prone to rupture and alert.
usually, the system self-decays and calms down over time, but in sepsis it gets out of control, causing more and more cells to rupture and die, and releasing more cytokines into the bloodstream.
when cells suddenly rupture, they release not only cytokines, but also other dangerous molecules called "alarm proteins" that warn the body of infection or damage and amplify ongoing cytokine storms.
UConn Health immunologist Vijay Rathinam wanted to know what alarm proteins were released when cells detected a bacterial molecule called lipid polysaccharose inside.
Ashley Russo, a graduate student at Rathinam Labs, worked with UConn Health immunologists Tony Vella and Antoine Menoret to classify the proteins released by these cells when they detected lipid polysaccharies.
they found something exciting.
Galectin-1 is a protein that binds to sugar and glycosin and appears to be emitted from cells.
interestingly, they found that galectin-1 was so small that it could even slip out of punctured holes in the cell membrane before the cell suddenly ruptured.
when they noticed this, they began to study the role of galectin-1 in sepsis.
found that galectin-1 appeared to inhibit the inflammatory response.
also found that mice lacking galectin-1 had lower levels of inflammation, less organ damage, and longer survival than normalized mice with bacterial infections and sepsis caused by polysaccharides.
to determine whether galectin-1 was released during sepsis in human patients, the team worked with Ph.D.s at Jena University Hospital.
Deshmukh, Bauer and Sponholz found that in the intensive care and healthy population, sepsis patients had higher levels of galectin-1 than other non-sepsis patients.
team is considering whether galectin-1 may be a drug target for cytokine storms during sepsis, and whether doctors can use it as a marker to identify seriously ill patients at risk.
() Source: Sugar-binding protein galectin-1 can be a biomarker for patients at risk of life threaten sepsis Original source: Ashley J. Russo et al, Intracellular immune sensing promoterings via gasdermin D-driven release of a lectin alarmin, Nature Immunology (2021). DOI: 10.1038/s41590-020-00844-7