Fig. 4: Local inflammation triggers the rapid accumulation of circulating monocyte-derived migrasomes at the site of inflammation.

a Mice were injected with CCR2-labeled migrasomes purified from mouse monocytes by i.v. injection After 30 min, mice were anesthetized with avertin (i.p., 375 mg/kg). LPS (500 ng/mL) combined with WGA were then injected into mouse liver using a syringe. Intravital imaging of the mouse liver was immediately performed to monitor CCR2-positive migrasomes. WGA labels localized injection sites and blood vessels. Scale bar, 20 μm. The right panel shows a statistical analysis of the relative fluorescence intensity of CCR2 at injection sites. Data are means ± SEM. n = 8 mice from three independent experiments. Two-tailed unpaired t-test was used for statistical analyses. b LPS (12 mg/kg) was injected into mice by i.p. injection. After 2 h, fluorescent antibodies against TNF-α and CCR2 were injected into mice by i.v. injection. After localized injection of LPS (500 ng/mL) and WGA, intravital imaging of the mouse liver was immediately performed to monitor CCR2-positive migrasomes. Scale bar, 20 μm. The right panel shows a statistical analysis of the relative fluorescence intensity of TNF-α at injection sites. Data are means ± SEM. n = 10 mice from three independent experiments. Two-tailed unpaired t-test was used for statistical analyses. c Intravital imaging of monocyte-derived migrasomes in WT and T9 KO mice liver after LPS stimulation as shown in b. Scale bar, 20 μm. The right panel shows a statistical analysis of the relative fluorescence intensity of TNF-α at injection sites. Data are means ± SEM. n = 10 mice from three independent experiments. Two-tailed unpaired t-test was used for statistical analyses. d Model for the role of monocyte-derived migrasomes in packaged release and targeted delivery of signaling ligands to the site of inflammation.