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Published online before print October 6, 2006

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(Journal of Leukocyte Biology. 2007;81:315-318.)
© 2007 by Society for Leukocyte Biology

The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection

Shamila Khan^*,, Nerida Cole^*,, Emma B. Hume^*,,,1, Linda Garthwaite, Timothy C. R. Conibear, David H. Miles^,, Yulina Aliwaga^*, Mark B. Krockenberger and Mark D. P. Willcox^*,,

^* Institute for Eye Research, Sydney, New South Wales Australia;
School of Optometry, University of New South Wales, Sydney, New South Wales, Australia;
Vision CRC, Sydney, New South Wales, Australia; and
Faculty of Veterinary Science, University of Sydney, New South Wales, Australia

¹Correspondence: Institute for Eye Research, University of New South Wales, Sydney, NSW 2052, Australia. E-mail: e.hume{at}ier.org.au

ABSTRACT

Pseudomonas is one of the leading causes of contact lens-related microbial keratitis. Despite the use of antibiotics, the host inflammatory response continues to cause damage to the cornea, which may lead to blindness. CXCR2-binding chemokines have been implicated in the pathogenesis of Pseudomonas keratitis, and the exact role of this receptor remains to be elucidated. Corneas of CXCR2 knockout and wild-type mice (Cmkar 2–/– and Cmkar 2+/+) were scratched, and 2 x 10⁶ CFU/mL Pseudomonas 6294 or 6206 was added to corneas. Twenty-four hours postinfection, mice were killed, and eyes were harvested for enumeration of bacteria, myeloperoxidase (MPO) levels, and inflammatory mediators. Cmkar 2–/– had 20- to 100-fold more bacteria than Cmkar 2+/+ mice. There were no differences in MPO levels between gene knockout and Cmkar 2+/+ mice. Histology revealed PMN were restricted to the limbal area. Levels of CXCR2 chemokines (keratinocyte-derived chemokine and MIP-2) were elevated significantly in gene knockout mice. A lack of CXCR2 leads to an inability to control bacterial numbers as a result of the inability of PMN to reach the site of infection in the avascular cornea. These results imply that CXCR2 is critical to the extravasation of neutrophils into the avascular cornea.

Key Words: cornea • gene knockout mice • microbial keratitis • CXCR2

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