Figure 3.
Glucocorticoids induce bone marrow migration of eosinophils. Circulating rhesus eosinophils were purified, labeled with 89Zr-oxine, and reinjected. PET/CT imaging was performed to track the location of the cells over time, with or without glucocorticoid administration. (A) Experimental design. Day 0 corresponds to the day of cell reinjection. Imaging on day 0 was performed immediately after reinjection (indicated by the 10-minute time point, which corresponds to the midpoint of the 20-minute imaging session), and 1 hour after reinjection. On day 1, animals in the treatment arm each received a single intravenous dose of glucocorticoid (GC, methylprednisolone 4 mg/kg), administered 30 minutes after BL PET imaging. Subsequent images were acquired hourly (counting from the time of BL imaging) for 4 hours. Control (Ctrl) animals were imaged serially at the same time points, without GC administration. Three independent experiments were performed per group, each on a different day in an unrelated adult rhesus macaque. The abbreviations and colors for each time point are preserved in the other panels of the figure to facilitate interpretation. (B) Live tracking of 89Zr-oxine–labeled eosinophils in the first hour after cell reinjection on day 0. Representative MIP PET/CT images at 10 minutes and 1 hour on day 0 are shown (top, SUV: standardized uptake value). The quantification of 89Zr distribution expressed as % ID with decay correction, is plotted for each organ at each imaging time point (bottom). These values indicate the percentage of the total 89Zr activity in a given organ’s volume, relative to the injected dose. (C) Live tracking of 89Zr-oxine labeled eosinophils in the absence (top) or presence (bottom) of glucocorticoid administration on day 1. Representative MIP PET/CT images at BL and 4 hours. (D) Sagittal and axial images of the spine in glucocorticoid-treated animals, before (BL) and after (4 hours) glucocorticoid injection. The red lines indicate the locations of the axial slice planes shown at the bottom. PET/CT images of 1 representative animal are shown. (E) Localization of 89Zr-oxine labeled eosinophils over time, with or without glucocorticoid administration. The x-axis is the time (in hours) after BL imaging. The y-axis displays 89Zr-oxine labeled eosinophil distribution, expressed as a decay-corrected percentage of the injected dose. Data are displayed separately for each of 4 organs: bone marrow, liver, lung, or spleen. Linear regression was performed separately for the 3 animals in the glucocorticoid arm and the 3 animals in the control arm. In both regressions, the response is organ 89Zr distribution (from the 89Zr-oxine labeled-eosinophils) expressed as a percentage of the injected dose; the regressors are the type of organ, the observation time point, and their interaction. The slope, or rate of change in each organ, is shown along with the P value from a Wald test indicative of whether the slope is significantly different from 0.