The role of CXC chemokine receptor 2 in Staphylococcus aureus keratitis

Cole, N; Hume, EBH; Khan, S; Garthwaite, L; Conibear, TCR; Willcox, MDP

The role of CXC chemokine receptor 2 in Staphylococcus aureus keratitis

Cole, N

Hume, EBH Khan, S Garthwaite, L Conibear, TCR Willcox, MDP

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Publication Type:: Journal Article
Citation:: Experimental Eye Research, 2014, 127 pp. 184 - 189
Issue Date:: 2014-01-01

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Field	Value	Language
dc.contributor.author	Cole, N https://orcid.org/0000-0002-9866-4694	en_US
dc.contributor.author	Hume, EBH	en_US
dc.contributor.author	Khan, S	en_US
dc.contributor.author	Garthwaite, L	en_US
dc.contributor.author	Conibear, TCR	en_US
dc.contributor.author	Willcox, MDP	en_US
dc.date.available	2014-07-07	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Experimental Eye Research, 2014, 127 pp. 184 - 189	en_US
dc.identifier.issn	0014-4835	en_US
dc.identifier.uri	http://hdl.handle.net/10453/37801
dc.description.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 1×108cfu/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. 24h 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. © 2014 Elsevier Ltd.	en_US
dc.relation.ispartof	Experimental Eye Research	en_US
dc.relation.isbasedon	10.1016/j.exer.2014.07.016	en_US
dc.subject.classification	Ophthalmology & Optometry	en_US
dc.subject.mesh	Cornea	en_US
dc.subject.mesh	Neutrophils	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Staphylococcus aureus	en_US
dc.subject.mesh	Eye Infections, Bacterial	en_US
dc.subject.mesh	Staphylococcal Infections	en_US
dc.subject.mesh	Corneal Ulcer	en_US
dc.subject.mesh	Peroxidase	en_US
dc.subject.mesh	Antigens, CD31	en_US
dc.subject.mesh	Vascular Cell Adhesion Molecule-1	en_US
dc.subject.mesh	Receptors, Interleukin-8B	en_US
dc.subject.mesh	RNA, Messenger	en_US
dc.subject.mesh	Enzyme-Linked Immunosorbent Assay	en_US
dc.subject.mesh	Real-Time Polymerase Chain Reaction	en_US
dc.subject.mesh	Platelet Endothelial Cell Adhesion Molecule-1	en_US
dc.title	The role of CXC chemokine receptor 2 in Staphylococcus aureus keratitis	en_US
dc.type	Journal Article
utslib.citation.volume	127	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1113 Opthalmology and Optometry	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	127	en_US

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 1×108cfu/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. 24h 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. © 2014 Elsevier Ltd.

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http://hdl.handle.net/10453/37801