Neutrophil Extracellular Traps (NETs) formation of Fcgr2b deficient mice in lupus mouse model with ischemic reperfusion injury

Abstract

Acute kidney injury (AKI) caused by renal ischemic reperfusion (I/R) is the most prevalent cause of morbidity and mortality in patients. Neutrophil extracellular traps (NETs) are important for the progression of lupus nephritis after renal I/R injury. Because neutrophils are the first immune cell that respond to tissue damage, neutrophils might be an important cell that determines renal I/R injury. Additionally, NET components, including cell-free DNA, histone, nucleosome, and cytoplasmic protein compartment release the auto-antigens that accelerate lupus disease activity. Therefore, this project aimed to compare NETs formation in several internal organs following renal I/R injury in Fcgr2b deficient (Fcgr2b-/-) mice, a lupus mouse model, and wildtype (WT) mice. At 24 h after I/R injury, Fcgr2b-/- mice had a higher level of NET biomarkers; PAD4, IL-1β expression, serum dsDNA, and the co-staining of neutrophil elastase (NE) with myeloperoxidase (MPO), in kidney and peripheral blood when compared with WT mice. Furthermore, the cell apoptosis activated caspase-3 in the kidney, serum anti-dsDNA, and immunoglobulin (IgG) deposition in glomeruli in Fcgr2b-/- mice at 120 h after I/R injury was also higher than the WT mice. Likewise, NETs formation and apoptosis Fcgr2b-/- neutrophils after stimulation with phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) were more prominent than WT neutrophils. These findings support that Fcgr2b-/- mice with renal I/R had a higher NETs formation, cell apoptosis in the kidney and in the remote organs that induced serum anti-dsDNA and accelerated lupus disease aggression.