Intravital imaging of neutrophil recruitment reveals the efficacy of FPR1 blockade in hepatic ischemia-reperfusion injury

摘要: Neutrophils are considered responsible for the pathophysiological changes resulting from hepatic ischemia-reperfusion (I/R) injury, which is a complication of trauma, shock, liver resection, and transplantation. Recently, evidence accumulating that formyl-peptide receptor (FPR) signaling constitutes an important danger signal guides neutrophils to sites inflammation. This study aimed investigate dynamic neutrophil recruitment using two-photon laser-scanning microscopy (TPLSM) in response FPR1 blockade during I/R. LysM-eGFP mice were subjected partial warm They pretreated with antagonist, cyclosporine H (CsH), or formyl peptide, fMLF. Liver was imaged after laser irradiation I/R TPLSM technique. CsH treatment alleviated as evidenced by decreased serum transaminase levels, reduced hepatocyte necrosis/apoptosis, diminished inflammatory cytokine, chemokine, oxidative stress. In contrast, systemic administration fMLF showed few effects. Time-lapse inhibited accumulation necrotic area induced vivo. CsH-treated group, number crawling velocity nonperfused lower than those control group. Meanwhile, did not affect monocyte/macrophage recruitment. Hepatic promoted retention their active behavior spleen, whereas prevented changes. Intravital revealed formyl-peptide-FPR1 regulating chemotaxis allow migration into Our findings suggest effective approaches elucidating mechanisms immune cell responses