PMID- 12861033 OWN - NLM STAT- MEDLINE DCOM- 20030812 LR - 20230216 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 83 IP - 7 DP - 2003 Jul TI - Involvement of macrophage chemotactic protein-1 and interleukin-1beta during inflammatory but not basic fibroblast growth factor-dependent neovascularization in the mouse cornea. PG - 927-38 AB - 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-1beta, on macrophage recruitment and neovascularization. Both MCP-1, IL-1beta 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-1beta was located in corneal epithelial cells and infiltrating inflammatory cells. In addition, double staining of corneas with antibodies specific for monocytes/macrophages and IL-1beta revealed that IL-1beta was found in infiltrating monocytes/macrophages at Day 2 after cauterization. Both IL-1beta and MCP-1 induced neovascularization in a rat cornea model, and the cauterization-induced corneal neovascularization was partially inhibited by subconjunctival injection of anti-IL-1beta 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-IL-1beta 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-1beta leading to inflammatory neovascularization. In addition, the IL-1beta and MCP-1 released from the corneal epithelial cells may directly induce corneal neovascularization. FAU - Yoshida, Shigeo AU - Yoshida S AD - Department of Ophthalmology, Kyushu University Graduate School of Medicine, Fukuoka, Japan. FAU - Yoshida, Ayako AU - Yoshida A FAU - Matsui, Hironori AU - Matsui H FAU - Takada, Yu-Ichiro AU - Takada Y FAU - Ishibashi, Tatsuro AU - Ishibashi T LA - eng PT - Journal Article PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 0 (Antibodies, Blocking) RN - 0 (Chemokine CCL4) RN - 0 (Interleukin-1) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (RNA, Messenger) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Antibodies, Blocking/pharmacology MH - Cell Movement/drug effects MH - Chemokine CCL4 MH - Cornea/*blood supply/drug effects/metabolism/pathology MH - Disease Models, Animal MH - Drug Synergism MH - Epithelium, Corneal/metabolism/pathology MH - Female MH - Fibroblast Growth Factor 2/*physiology MH - In Situ Hybridization MH - Interleukin-1/genetics/immunology/*metabolism/pharmacology MH - Macrophage Inflammatory Proteins/genetics/immunology/*metabolism/pharmacology MH - Macrophages/drug effects/physiology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Neovascularization, Pathologic/*metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley EDAT- 2003/07/16 05:00 MHDA- 2003/08/13 05:00 CRDT- 2003/07/16 05:00 PHST- 2003/07/16 05:00 [pubmed] PHST- 2003/08/13 05:00 [medline] PHST- 2003/07/16 05:00 [entrez] AID - S0023-6837(22)03492-4 [pii] AID - 10.1097/01.lab.0000075642.11787.83 [doi] PST - ppublish SO - Lab Invest. 2003 Jul;83(7):927-38. doi: 10.1097/01.lab.0000075642.11787.83.