TY - JOUR
T1 - Endothelial Monocyte Activating Polypeptide II inhibits lung neovascularization and airway epithelial morphogenesis
AU - Schwarz, Margaret A.
AU - Zhang, Fangrong
AU - Gebb, Sarah
AU - Starnes, Vaughn
AU - Warburton, David
N1 - Funding Information:
The authors would like to acknowledge the technical assistance of Yangsun Jin. The research was supported in part by a Grant in Aid from the American Heart Association 1131-GI1 (M.A.S.), American Lung Association RG-084-N (M.A.S.), NIH HL-60061 (M.A.S.), NIH HL-03981 (M.A.S.), Children's Hospital Research Institute RCDA (M.A.S.), NIH HL-44060 (D.W.), NIH HL-44977 (D.W.), and NIH HL-60231 (D.W.).
PY - 2000/7/1
Y1 - 2000/7/1
N2 - Neovascularization is crucial to lung development and is mediated through a variety of angiogenic and anti-angiogenic factors. Herein, we show that excess Endothelial Monocyte Activating Polypeptide (EMAP) II, an anti-angiogenic protein, not only inhibits fetal lung neovascularization, but also significantly alters airway epithelial morphogenesis. In a murine allograft model of lung neovascularization and morphogenesis, embryonic lungs transplanted under the skin of immunocompromised mice receiving intraperitoneal EMAP II, had a 56% reduction in vessel density (P<0.0001) compared to control. EMAP II treated lung transplants also exhibited a marked alteration in lung morphogenesis, including lack of type II alveolar cell formation, determined by markedly decreased expression of surfactant protein C, and increased apoptosis. In contrast, lung implants in animals receiving an EMAP II blocking antibody had an increase in vessel density of 50% (P<0.0001) and increased expression of surfactant protein C mRNA in distal epithelium. These studies demonstrate that EMAP II negatively modulates lung neovascularization as well as leading to the arrest of lung airway epithelial morphogenesis and apoptosis. Copyright (C) 2000 Elsevier Science Ireland Ltd.
AB - Neovascularization is crucial to lung development and is mediated through a variety of angiogenic and anti-angiogenic factors. Herein, we show that excess Endothelial Monocyte Activating Polypeptide (EMAP) II, an anti-angiogenic protein, not only inhibits fetal lung neovascularization, but also significantly alters airway epithelial morphogenesis. In a murine allograft model of lung neovascularization and morphogenesis, embryonic lungs transplanted under the skin of immunocompromised mice receiving intraperitoneal EMAP II, had a 56% reduction in vessel density (P<0.0001) compared to control. EMAP II treated lung transplants also exhibited a marked alteration in lung morphogenesis, including lack of type II alveolar cell formation, determined by markedly decreased expression of surfactant protein C, and increased apoptosis. In contrast, lung implants in animals receiving an EMAP II blocking antibody had an increase in vessel density of 50% (P<0.0001) and increased expression of surfactant protein C mRNA in distal epithelium. These studies demonstrate that EMAP II negatively modulates lung neovascularization as well as leading to the arrest of lung airway epithelial morphogenesis and apoptosis. Copyright (C) 2000 Elsevier Science Ireland Ltd.
KW - Angiogenesis
KW - Anti-angiogenesis
KW - Endothelial Monocyte Activating Polypeptide II
KW - Lung morphogenesis
KW - Neovascularization
KW - Pulmonary microvasculature
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U2 - 10.1016/S0925-4773(00)00361-0
DO - 10.1016/S0925-4773(00)00361-0
M3 - Article
C2 - 10906456
AN - SCOPUS:0034234724
SN - 0925-4773
VL - 95
SP - 123
EP - 132
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1-2
ER -