Reduced leukocyte migration, but normal rolling and arrest, in interleukin-8 receptor homologue knockout mice.
OBJECTIVE
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.
Becker
M D
MD
Department of Ophthalmology, Casey Eye Institute, Oregon Health Sciences University, Portland 97201, USA. beckemat@ohsu.edu
O'Rourke
L M
LM
Blackman
W S
WS
Planck
S R
SR
Rosenbaum
J T
JT
D000818:Animals; D002465:Cell Movement; D004926:Escherichia coli; D005260:Female; D007498:Iris / Q000098:blood supply*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology*; D023063:Receptors, Interleukin-8B; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000276:immunology*; D014822:Vitreous Body / Q000187:drug effects
D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D023063:Receptors, Interleukin-8B