Chemokine receptor inhibition alters ¹¹¹In-leukocyte trafficking in normal rats

Objectives Effects of antileukinate (AL), a hexapeptide inhibitor of chemokine receptors CXCR1 & CXCR2, on neutrophil trafficking in inflammation are well documented; data on effects in normals are scant. This investigation used ¹¹¹In-labeled leukocytes (InWBC) to investigate AL effects on leukocyte trafficking in normal rats.

Methods Two groups of normal adult Fisher 344 rats were studied: Controls (n=8) & AL treated (ALRx)(n=4). 20 mL blood was withdrawn from donor rats, & leukocytes labeled in vitro with ¹¹¹In-oxine. Controls received 3.7-4.6 MBq InWBC. For ALRx, 6 mg AL was incubated with InWBC in vitro for 15 min before InWBC injection. InWBC labeling efficiency & viability were determined. Ante-mortem imaging, euthanasia & tissue collection to measure percent activity & myeloperoxidase (MPO) in various organs, were done 24 hrs post injection.

Results Labeling efficiency & cell viability were not statistically different between groups (p>0.05). Percent activity in ALRx compared to Controls was significantly higher in heart, lung, liver, kidney, marrow, & intestine, & significantly lower in spleen. MPO values were significantly increased in ALRx kidney & liver (p<0.05). Control images showed activity limited to the reticuloendothelial system (RES). ALRx images showed RES activity & diffusely increased soft tissue activity & faint renal activity.

Conclusions The data indicate that, besides interrupting their chemotactic response in inflammation, CXCR1 & CXCR2 blockade affects normal leukocyte trafficking, by decreasing splenic accumulation causing redistribution to other organs. The mechanism by which this occurs warrants further investigation

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