title: The role of CXC chemokine receptor 2 in Staphylococcus aureus keratitis.
abstract: Staphylococcus aureus is a leading cause of corneal infection. CXC receptor 2 binding chemokines have been implicated in the pathogenesis of Pseudomonas aeruginosa keratitis. The role of this receptor in immune responses during Staphylococcus keratitis remains to be fully understood. Corneas of CXC receptor 2 knockout and wild-type mice (Cmkar -/- & Cmkar +/+) were scratched and 1 × 10(8) cfu/ml of strain Staph 38 applied. Twenty-four hours post-infection, mice were sacrificed and eyes harvested for enumeration of bacteria and measurement of myeloperoxidase levels. Production of inflammatory mediators, cellular adhesion molecules and chemokines in response to infection were investigated by ELISA, and PCR. 24 h after challenge with S. aureus, Cmkar -/- mice had developed a more severe response with a 50-fold higher bacterial load than WT mice. PMNs failed to penetrate the corneas of Cmkar -/- mice. However, concentrations of KC, MIP-2, IL-1β and IL-6 were significantly elevated (6-13 fold) in Cmkar-/- mice. The concentration of LTB4 was decreased (2 fold). Cmkar-/- mice failed to upregulate mRNA for VCAM-1 or PECAM-1 in response to infection, but had constitutively higher levels of ICAM-1. A lack of CXC receptor 2 lead to an inability to control bacterial numbers as a result of failure of PMNs to penetrate the cornea to the site of infection, even when chemokines were more highly produced. These results imply that CXCR2-mediated signaling through upregulation of adhesion molecules is essential to margination of PMNs in this infection model.
authors.affiliation: School of Chemistry and Forensic Science, University of Technology, Sydney, Ultimo 2007, Australia; School of Optometry, University of New South Wales, Sydney, 2052, Australia.
authors.forename: Nerida
authors.initials: N
authors.lastname: Cole
authors.affiliation: School of Optometry, University of New South Wales, Sydney, 2052, Australia; Brien Holden Vision Institute, UNSW, Sydney, 2052, Australia.
authors.forename: Emma B H
authors.initials: EB
authors.lastname: Hume
authors.affiliation: School of Optometry, University of New South Wales, Sydney, 2052, Australia; Brien Holden Vision Institute, UNSW, Sydney, 2052, Australia.
authors.forename: Shamila
authors.initials: S
authors.lastname: Khan
authors.affiliation: Brien Holden Vision Institute, UNSW, Sydney, 2052, Australia.
authors.forename: Linda
authors.initials: L
authors.lastname: Garthwaite
authors.affiliation: School of Optometry, University of New South Wales, Sydney, 2052, Australia; Brien Holden Vision Institute, UNSW, Sydney, 2052, Australia.
authors.forename: Tim C R
authors.initials: TC
authors.lastname: Conibear
authors.affiliation: School of Optometry, University of New South Wales, Sydney, 2052, Australia. Electronic address: m.willcox@unsw.edu.au.
authors.forename: Mark D P
authors.initials: MD
authors.lastname: Willcox
mesh_terms: D000818:Animals; D003315:Cornea / Q000382:microbiology; D003320:Corneal Ulcer / Q000378:metabolism* / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D015818:Eye Infections, Bacterial / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D023063:Receptors, Interleukin-8B / Q000502:physiology*; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B; D019010:Vascular Cell Adhesion Molecule-1; D009195:Peroxidase
keywords: CXC receptor 2; Staphylococcus aureus; cornea; gene knockout mice