Reduced leukocyte migration, but normal rolling and arrest, in interleukin-8 receptor homologue knockout mice

PURPOSE. TO determine the role of the murine interleukin-8 receptor homolog ue (mIL8Rh, neutrophil chemokine CXC receptor 2) in leukocyte migration usi ng intravital microscopy in a standardized model of eye inflammation, endot oxin-induced uveitis (EIU). METHODS. Two hundred rifty nanograms of E. coli endotoxin was injected into the vitreous of knockout mILa-8Rh(-/-) (n = 7) mice or heterozygous litter mate mIL-8Rh(+/-) controls (n = 7). Intravital microscopic examination of i ris microvasculature was performed at baseline and 6 and 24 hours after end otoxin injection. The numbers of rolling (cells/mm(2) endothelial surface/m in), sticking (cells/mm2 endothelial surface), and infiltrating cells (cell s/mm2 iris tissue) were evaluated by digital off-line quantification. RESULTS. The number of infiltrating cells was significantly reduced in mIL- 8Rh(-/-) mice: 406 +/- 77 cells/mm(2) at 6 hours and 242 +/- 50 cells/mm2 a t 24 hours in mIL-8Rh(+/-) mice versus 14 +/- 4 cells/mm(2) at 6 hours and 38 +/- 11 cells/mm(2) at 24 hours in mIL-8R(h-/-) mise (P < 0.001). In cont rast, the absence of the IL-8 receptor homologue did not reduce rolling or sticking, CONCLUSIONS. Iris rhodamine angiography allows precise quantification of le ukocyte- endothelial dynamics in the absence of surgical trauma. IL-8 and i ts homologues are known to be potent signals for leukocyte migration. Altho ugh IL-8 has previously been implicated in cell adhesion, video imaging in vivo demonstrated that deletion of the IL-8 receptor homologue had minimal effect on rolling or arrest in this model of inflammation.