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

Matthias D. Becker, Leslie M. O'Rourke, Whitney S. Blackman, Stephen R. Planck, James T. Rosenbaum

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

PURPOSE. To determine the role of the murine interleukin-8 receptor homologue (mIL-8Rh, neutrophil chemokine CXC receptor 2) in leukocyte migration using intravital microscopy in a standardized model of eye inflammation, endotoxin-induced uveitis (EIU). METHODS. Two hundred fifty nanograms of E. coli endotoxin was injected into the vitreous of knockout mIL-8Rh(-/-) (n = 7) mice or heterozygous littermate mIL-8Rh(+/-) controls (n = 7). Intravital microscopic examination of iris microvasculature was performed at baseline and 6 and 24 hours after endotoxin injection. The numbers of rolling (cells/mm2 endothelial surface/min), sticking (cells/mm2 endothelial surface), and infiltrating cells (cells/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/mm2 at 6 hours and 242 ± 50 cells/mm2 at 24 hours in mIL-8Rh(+/-) mice versus 14 ± 4 cells/mm2 at 6 hours and 38 ± 11 cells/mm2 at 24 hours in mIL-8Rh(-/-) mice (P < 0.001). In contrast, the absence of the IL-8 receptor homologue did not reduce rolling or sticking. CONCLUSIONS. Iris rhodamine angiography allows precise quantification of leukocyte endothelial dynamics in the absence of surgical trauma. IL-8 and its homologues are known to be potent signals for leukocyte migration. Although 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.

Original languageEnglish (US)
Pages (from-to)1812-1817
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume41
Issue number7
StatePublished - Jun 26 2000

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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