The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection.
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 2x10(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.
Khan
Shamila
S
Intitute for Eye Research, and School of Optometry, University of New South Wales, Sydney, NSW 2052, Australia.
Cole
Nerida
N
Hume
Emma B
EB
Garthwaite
Linda
L
Conibear
Timothy C R
TC
Miles
David H
DH
Aliwaga
Yulina
Y
Krockenberger
Mark B
MB
Willcox
Mark D P
MD
D000818:Animals; D003315:Cornea / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000502:physiology*
D018836:Inflammation Mediators; D023063:Receptors, Interleukin-8B