“These nanoparticles can help maintain white blood cells’ regular function to combat virus infection,” mentioned Changcheng Zhou, a professor of biomedical sciences within the UCR School of Medicine, who co-led the analysis with Tzung Okay. Hsiai, a professor of drugs and bioengineering at UCLA.
Zhou defined that macrophages function frontline immune cells in response to SARS-CoV-2 an infection by recognizing and swallowing up viruses. These cells additionally produce cytokines, which is a crucial a part of the physique’s immune response however can turn out to be uncontrolled.
The virus-induced cytokine storm the flooding by the immune system of the bloodstream with inflammatory proteins referred to as cytokines that follows an an infection can kill tissue and harm organs.
Zhou mentioned infected macrophages might infiltrate completely different tissues to trigger hostile results related to COVID-19, comparable to myocarditis or coronary heart irritation.
“Our findings can potentially be used to treat COVID-19-associated diseases, including heart disease,” he mentioned.
“In addition to lung inflammation or injury, approximately 15% of COVID-19 patients with pre-existing conditions may develop acute cardiac arrhythmia and myocarditis, and macrophages may play an important role in this process.”
Mechanisms underlying SARS-CoV-2-mediated macrophage dysfunctions are usually not solely recognized to scientists. According to Zhou, it’s because many immune cells, together with macrophages, have low expression ranges of human ACE2, or hACE2, the receptor for SARS-CoV-2.
“Previous studies in this line of work have mainly focused on hACE2-dependent mechanisms,” he mentioned. “Our results, on the other hand, suggest that SARS-CoV-2 can hijack macrophages and induce inflammatory responses even without hACE2.”
Zhou and his staff explored neutralizing SARS-CoV-2 with liposome particles as an progressive therapeutic technique for treating COVID-19-associated illnesses. The staff used nanoparticles to engineer “Liposome-hACE2” as a decoy.
“The SARS-CoV-2 virus binds to hACE2 on the surface of the liposomes instead of immune cells, preventing it from leading to macrophage-mediated inflammation,” Zhou mentioned.
“It is also possible that Liposome-hACE2, with or without SARS-CoV-2 binding, can be internalized by macrophages, which can inhibit SARS-CoV-2 viral particle replication. This contributes to decreased inflammatory responses.”
The analyses had been finished on macrophages in people and mice. In murine tissue, the researchers discovered that the molecular traps inhibited SARS-CoV-2 Spike protein-induced macrophage infiltration within the lung and coronary heart, suppressing lung and cardiac irritation.
Spike protein stimulated irritation by activating a signalling pathway referred to as NF-κB.
“The nanoparticles we developed are very efficient against virus-induced inflammation,” Zhou mentioned.
“Deletion of IκB kinase β, a key regulator for NF-κB signalling, can abolish Spike protein-induced macrophage inflammatory responses. IκB kinase β is, therefore, essential for virus-induced macrophage inflammation. It could be an important target to combat the SARS-CoV-2 virus.”
The analysis was funded by the American Heart Association and the National Heart, Lung, and Blood Institute.