A critical role for CCL2 and CCL3 chemokines in the regulation of polymorphonuclear neutrophils recruitment during corneal infection in mice.
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.
Xue
Mei-Lang
ML
Vision Cooperative Research Centre, Sydney, NSW, Australia.
Thakur
Archana
A
Cole
Nerida
N
Lloyd
Andrew
A
Stapleton
Fiona
F
Wakefield
Denis
D
Willcox
Mark D P
MD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000378:metabolism / Q000502:physiology*; D054405:Chemokine CCL3 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007634:Keratitis / Q000276:immunology* / Q000382:microbiology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D054389:Receptors, CCR1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; C515301:Ccr1 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054389:Receptors, CCR1; D011994:Recombinant Proteins