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A small subgroup of blood cells called basophilic granulocytes has been known mainly for their role in allergies and asthma. Dr. Gabriele Schramm, a scientist at the ARCN partner institution Research Center Borstel, has long been investigating that basophils can do more than cause allergies in her laboratory.
In collaboration with the scientific teams of Heidelberg University Hospital, Friedrich Alexander University Erlangen-Nuremberg, and Forschungszentrum Borstel, it has now been found that basophilic granulocytes are indeed also significantly involved in the healing process after a heart attack. These cells migrate into the area of inflammation after an infarction and, after activation, release cellular messenger substances (interleukin (IL-) 4 and IL-13), which cause the conversion of pro-inflammatory into anti-inflammatory phagocytes. The latter activate the body's repair system and thus wound healing. In an animal model, the researchers showed for the first time that basophils are very important for rapid and efficient recovery: in mice lacking basophils, the healing process was significantly worse. Consistent with this, patients who had few basophils at the time of infarction had a considerably worse prognosis.
Interestingly, the basophil-mediated healing process was further enhanced by treating the animals with IPSE/alpha-1, a molecule that leads to the release of the messengers IL-4 and IL-13 from basophils. This molecule is naturally produced by eggs of the parasitic worm Schistosoma mansoni. At the Borstel Research Center, research on the anti-inflammatory effect of factors from parasitic worms on the host immune system has been successfully conducted for many years. "The eggs of this parasite perforate the intestinal wall, which would result in massive inflammation due to the influx of intestinal bacteria," explains Dr. Schramm. "However, this inflammation is prevented by the release of IPSE/alpha-1 and the resulting release of IL-4 and IL-13 from the basophils: the pro-inflammatory phagocytes are defused, so to speak, and wound healing, and repair processes are triggered instead. So it made sense to use the anti-inflammatory effects of this factor to dampen other inflammatory processes and diseases." And indeed, treating the mice with IPSE/alpha-1 after infarction resulted in faster and better healing via the enhanced release of IL-4 and IL-13.
Future studies will show whether this molecule can also be used in humans for treatment after infarction and other diseases with excessive immune response and inflammation, such as asthma, allergies, and autoimmune diseases.
Original publication: Basophils balance healing after myocardial infarction via IL-4/IL-13
Florian Sicklinger, Ingmar Sören Meyer, Xue Li, Daniel Radtke, Severin Dicks, Moritz P Kornadt, Christina Mertens, Julia K Meier, Kory J Lavine, Yunhang Zhang, Tim Christian Kuhn, Tobias Terzer, Jyoti Patel, Melanie Boerries, Gabriele Schramm, Norbert Frey, Hugo A Katus, David Voehringer, Florian Leuschner. J Clin Invest. 2021 Jul 1;131(13):e136778. doi: 10.1172/JCI136778:
