Macrophage inflammatory protein-2 and vascular endothelial growth factor regulate corneal neovascularization induced by infection with Pseudomonas aeruginosa in mice.
Pseudomonas aeruginosa ocular infection causes extensive corneal neovascularization. The purpose of the present study was to investigate the role of the angiogenic factors macrophage inflammatory protein-2 (MIP-2) and vascular endothelial growth factor (VEGF) in the regulation of corneal neovascularization during P. aeruginosa ocular infection. After administering anti-MIP-2 antibody or control antibody, mouse corneas were challenged with P. aeruginosa. The expression of MIP-2 and VEGF was detected using an ELISA from ocular homogenates. Corneal neovascularization was examined by histology. The cellular sources of MIP-2 and VEGF were identified by immunohistochemistry. In addition, protein expression of MIP-2 and VEGF in isolated corneas was measured to determine the ability of the cornea to produce these two mediators. Results showed that the expression of MIP-2 and VEGF was significantly (P < 0.05) elevated after bacterial infection, and high levels of these two mediators paralleled the extensive corneal neovascularization seen at later stages of the infection. Anti-MIP-2 antibody treatment resulted in a significant (P < 0.05) reduction in VEGF expression and in corneal neovascularization. Both corneal resident cells and infiltrating neutrophils had the ability to produce MIP-2 and VEGF after stimulation. The present study demonstrates that both MIP-2 and VEGF are important mediators in the regulation of corneal neovascularization caused by P. aeruginosa infection, and that MIP-2 regulates the production of VEGF.
Cooperative Research Centre for Eye Research and Technology, School of Optometry and Vision Science, University of New South Wales, Sydney, New South Wales, Australia.
Mei-Lang
ML
Xue
Archana
A
Thakur
Mark
M
Willcox
D000818:Animals; D054426:Chemokine CXCL2; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000276:immunology / Q000502:physiology*; D015818:Eye Infections, Bacterial / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology / Q000502:physiology*; D008222:Lymphokines / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000276:immunology / Q000502:physiology*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000473:pathology*; D011550:Pseudomonas aeruginosa; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D054426:Chemokine CXCL2; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D015846:Monokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors