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The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection
Author(s) -
Khan Shamila,
Cole Nerida,
Hume Emma B.,
Garthwaite Linda,
Conibear Timothy C. R.,
Miles David H.,
Aliwaga Yulina,
Krockenberger Mark B.,
Willcox Mark D. P.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0506344
Subject(s) - biology , cxc chemokine receptors , keratitis , microbiology and biotechnology , cornea , chemokine , pseudomonas aeruginosa , immunology , chemokine receptor , inflammation , bacteria , genetics , neuroscience
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 × 10 6 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.