TY - JOUR
T1 - Role of MCP-1 and MIP-1α in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization
AU - Yoshida, Shigeo
AU - Yoshida, Ayako
AU - Ishibashi, Tatsuro
AU - Elner, Susan G.
AU - Elner, Victor M.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Macrophages are important participants in neovascularization. This study was designed to examine the role of the monocyte/macrophage chemotactic proteins, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in a mouse model of oxygen-induced ischemic retinopathy and to determine whether the morphology and distribution of macrophages/microglia are concomitantly altered. The MCP-1, MIP-1α mRNA levels increased at 3 h after ischemia. MCP-1, MIP-1α, and vascular endothelial growth factor protein levels were also increased markedly and were maximal on days 1, 0.5, and 1, respectively, after ischemia. In situ hybridization showed that MCP-1 and MIP-1α were localized in the hypoxic inner retina. Immunostaining demonstrated that the macrophages/microglia in the retina had morphological changes with enlarged processes, and some were closely associated with neovascular tufts at postnatal day 17. Coadministration of the neutralizing antibodies against MCP-1 and MIP-1α inhibited retinal neovascularization by 30%. Our data suggest that MCP-1 and MIP-1α are involved in the induction of retinal neovascularization and play a role in the inflammation induced by the ischemic retinopathy, possibly by modulating or attracting macrophages/microglia.
AB - Macrophages are important participants in neovascularization. This study was designed to examine the role of the monocyte/macrophage chemotactic proteins, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in a mouse model of oxygen-induced ischemic retinopathy and to determine whether the morphology and distribution of macrophages/microglia are concomitantly altered. The MCP-1, MIP-1α mRNA levels increased at 3 h after ischemia. MCP-1, MIP-1α, and vascular endothelial growth factor protein levels were also increased markedly and were maximal on days 1, 0.5, and 1, respectively, after ischemia. In situ hybridization showed that MCP-1 and MIP-1α were localized in the hypoxic inner retina. Immunostaining demonstrated that the macrophages/microglia in the retina had morphological changes with enlarged processes, and some were closely associated with neovascular tufts at postnatal day 17. Coadministration of the neutralizing antibodies against MCP-1 and MIP-1α inhibited retinal neovascularization by 30%. Our data suggest that MCP-1 and MIP-1α are involved in the induction of retinal neovascularization and play a role in the inflammation induced by the ischemic retinopathy, possibly by modulating or attracting macrophages/microglia.
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U2 - 10.1189/jlb.0302117
DO - 10.1189/jlb.0302117
M3 - Article
C2 - 12525571
AN - SCOPUS:0037241365
VL - 73
SP - 137
EP - 144
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -