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Induction of macrophage inflammatory protein-1α and vascular endothelial growth factor during inflammatory neovascularization in the mouse cornea

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Abstract

We predicted that the appearance of macrophages in inflammatory areas is necessary for angiogenic responses in various inflammatory diseases. Using a mouse inflammatory corneal model in which model mouse corneas were cauterized with silver nitrate, we examined the infiltration of macrophages immunohistochemically and the total area of neovascularization quantitively. The expression of macrophage inflammatory protein-1α (MIP-1α) and vascular endothelial growth factor (VEGF) levels were also examined. A day after cauterization, short capillaries began to develop into the corneal stroma, and after 4 or 5 days the neovascularization became maximal and then began to regress. The number of macrophages within the cauterized cornea increased to a maximum at day 3 and began to decrease at day 5. The number of infiltrated macrophages reached maximum at day 3. Both MIP-1α and VEGF protein levels increased markedly immediately after the chemical cauterization, and production of MIP-1α (85.8 pg/4 corneas) and VEGF (206.5 pg/4 corneas) was maximal at 1 day and 0.5 day after cauterization, respectively. MIP-1α and VEGF mRNA levels also increased at 0.5 day after cauterization. In situ hybridization showed that MIP-1α was localized in corneal epithelial cells, and VEGF was localized in corneal epithelial cells and infiltrating inflammatory cells. MIP-1α and VEGF may have an important role in recruiting macrophages and neovascularization.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, 812-8582, Japan

    Soh-ichiro Ogawa, Shigeo Yoshida, Mayumi Ono & Michihiko Kuwano

  2. Department of Pharmacology and Cell Signaling, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, 812-8582, Japan

    Hitoshi Onoue & Yushi Ito

  3. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka, 812-8582, Japan

    Tatsuro Ishibashi & Hajime Inomata

Authors
  1. Soh-ichiro Ogawa
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  2. Shigeo Yoshida
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  3. Mayumi Ono
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  4. Hitoshi Onoue
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  6. Tatsuro Ishibashi
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  7. Hajime Inomata
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  8. Michihiko Kuwano
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Ogawa, Si., Yoshida, S., Ono, M. et al. Induction of macrophage inflammatory protein-1α and vascular endothelial growth factor during inflammatory neovascularization in the mouse cornea. Angiogenesis 3, 327–334 (1999). https://doi.org/10.1023/A:1026554404941

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