1. ¹Vision Cooperative Research Centre, Sydney, NSW, Australia
2. ²The School of Optometry and Vision Science, The University of New South Wales, Sydney, NSW, Australia
3. ³Institute for Eye Research, Sydney, NSW, Australia
4. ⁴Inflammatory Diseases Research Unit, School of Pathology, The University of New South Wales, Sydney, NSW, Australia

Correspondence: Professor MDP Willcox, Institute for Eye Research, The University of New South Wales, Rupert Myers Building, Sydney, NSW 2052, Australia. E-mail: m.willcox@ier.org.au

⁵These two authors contributed equally to this work.

⁶Present address: Department of Pathology, Wayne State University Karmanos Cancer Institute, Detroit, MI, USA.

Received 24 August 2006; Revised 1 May 2007; Accepted 4 May 2007; Published online 19 June 2007.

Abstract

While the role of CC chemokines in mononuclear cell trafficking and activation has been well studied, the functional role of CC chemokines in the regulation of polymorphonuclear neutrophil (PMN) recruitment in vivo has not been widely examined. Bacterial infection of the cornea (keratitis) is a relatively common, sometimes sight-threatening disease, which features acute inflammation with ulceration and PMN infiltration. Here, we demonstrate a critical role for the chemokines, CCL2 and CCL3, in the Pseudomonas aeruginosa-induced model of corneal infection in BALB/c mice. Treatment of mice with anti-CCL2 or anti-CCL3 antibodies resulted in a significant reduction in severity of corneal damage and PMN infiltration at 1 and 7 days after infection compared to control antibody-treated eyes, but did not significantly alter the rate of bacterial clearance from the cornea. Our findings provide strong evidence that CCL2 and CCL3 are critical regulators of PMN recruitment, and may lead to therapeutic strategies via targeting of the CC chemokines, CCL2 and CCL3, in the management of P. aeruginosa keratitis.