Involvement of macrophage chemotactic protein-1 and interleukin-1β during inflammatory but not basic fibroblast growth factor-dependent neovascularization in the mouse cornea

Shigeo Yoshida, Ayako Yoshida, Hironori Matsui, Yu ichiro Takada, Tatsuro Ishibashi

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Corneal neovascularization develops in several pathologic conditions, but its underlying mechanisms remain elusive. We used a mouse inflammatory corneal model (corneas cauterized with silver nitrate) and assessed the role of monocyte/macrophage-attracting factors, macrophage chemotactic protein-1 (MCP-1), and a proinflammatory cytokine, IL-1β, on macrophage recruitment and neovascularization. Both MCP-1, IL-1β protein, and mRNA levels increased markedly 12 hours after the chemical cauterization. In situ hybridization showed that MCP-1 was located in corneal epithelial cells, and IL-1β was located in corneal epithelial cells and infiltrating inflammatory cells. In addition, double staining of corneas with antibodies specific for monocytes/macrophages and IL-1β revealed that IL-1β was found in infiltrating monocytes/macrophages at Day 2 after cauterization. Both IL-1β and MCP-1 induced neovascularization in a rat cornea model, and the cauterization-induced corneal neovascularization was partially inhibited by subconjunctival injection of anti-1L-1β or anti-MCP-1. Coadministration of two antibodies inhibited corneal neovascularization slightly more than that by the administration of each. In contrast, administration of the anti-MCP-1 or anti-1L-1β showed minimal inhibition of basic fibroblast growth factor-driven corneal neovascularization by mouse cornea assay. Cauterized corneas treated with anti-MCP-1 antibody had significantly fewer monocytes/macrophages than control. These results indicate the existence of distinct monocyte/macrophage-involved angiogenic pathways in mouse cornea, in which MCP-1 released from corneal epithelial cells attracts monocytes/macrophages into the cornea, where they release IL-1β leading to inflammatory neovascularization. In addition, the IL-1β and MCP-1 released from the corneal epithelial cells may directly induce corneal neovascularization.

Original languageEnglish
Pages (from-to)927-938
Number of pages12
JournalLaboratory Investigation
Volume83
Issue number7
DOIs
Publication statusPublished - Jul 1 2003

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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