title: Relationship between complement membrane attack complex, chemokine (C-C motif) ligand 2 (CCL2) and vascular endothelial growth factor in mouse model of laser-induced choroidal neovascularization.
abstract: The present study investigated the interactions among the complement membrane attack complex (MAC), CCL2, and VEGF that occur in vivo during the development of choroidal neovascularization (CNV). We first investigated the sequential expression of MAC, CCL2, and VEGF during laser-induced CNV in C57BL/6 mice. Increased MAC deposition was detected at 1 h, CCL2 increased at 3 h, and VEGF was up-regulated at day 3 post-laser treatment. These results suggested that during laser-induced CNV, MAC, CCL2 and VEGF are formed and/or expressed in the following order: MAC → CCL2 → VEGF. To determine the cross-talk between MAC, CCL2, and VEGF during laser-induced CNV, neutralizing antibodies were injected both systemically and locally to block the bioactivity of each molecule. Blocking MAC formation inhibited CCL2 and VEGF expression and also limited CNV formation, whereas neutralization of CCL2 bioactivity did not affect MAC deposition; however, it reduced VEGF expression and CNV formation. When bioactivity of VEGF was blocked, CNV formation was significantly inhibited, but MAC deposition was not affected. Together, our results demonstrate that MAC is an upstream mediator and effect of MAC on the development of laser-induced CNV can be attributed to its direct effect on VEGF as well as its effect on VEGF that is mediated by CCL2. Understanding the interplay between immune mediators is critical to gain insight into the pathogenesis of CNV.
authors.affiliation: Department of Ophthalmology, University of Arkansas for Medical Sciences, Little Rock, Arizona 72205, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.forename: Valeriy V
authors.initials: VV
authors.lastname: Lyzogubov
authors.forename: Ruslana G
authors.initials: RG
authors.lastname: Tytarenko
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007834:Lasers / Q000009:adverse effects*; D051379:Mice; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D057134:Antibodies, Neutralizing; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015938:Complement Membrane Attack Complex; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse