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Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis
Masako Yasuda1, Shunichi Shimizu, Kyoko Ohhinata
1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Abstract:
Ets-1, which stimulates metalloproteinase gene transcription, has a key role in angiogenesis. We first examined whether activated polymorphonuclear leukocytes (PMNs) enhanced angiogenesis through the induction of Ets-1. Addition of activated PMNs to endothelial cells stimulated both in vitro angiogenesis in collagen gel and Ets-1 expression. Both angiogenesis and Ets-1 expression induced by PMNs were reduced by ets-1 antisense oligonucleotide, suggesting that Ets-1 is an important factor in PMN-induced angiogenesis. Although intercellular adhesion molecule (ICAM)-1 and E-selectin are involved in PMN-induced angiogenesis, the mechanisms underlying their roles in angiogenesis have yet to be elucidated. PMN-induced Ets-1 expression was reduced by a monoclonal antibody against ICAM-1 but not E-selectin despite the inhibition of PMN-induced angiogenesis by both antibodies. Moreover, the stimulation of angiogenesis by H(2)O(2) without PMNs was inhibited by a monoclonal antibody to E-selectin but not ICAM-1. These findings suggested that ICAM-1 in endothelial cells may act as a signaling receptor to induce Ets-1 expression, whereas E-selectin seems to function in the formation of tubelike structures in vascular endothelial cell cultures.
Insights
Activated polymorphonuclear leukocytes (PMNs) promote angiogenesis by inducing Ets-1. Intercellular adhesion molecule-1 (ICAM-1) signals Ets-1, while E-selectin aids in blood vessel formation.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Ets-1 is crucial for metalloproteinase gene transcription and angiogenesis.
- Polymorphonuclear leukocytes (PMNs) are implicated in angiogenesis, but their precise mechanisms are unclear.
Purpose of the Study:
- To investigate if activated PMNs enhance angiogenesis via Ets-1 induction.
- To elucidate the roles of Intercellular Adhesion Molecule-1 (ICAM-1) and E-selectin in PMN-induced angiogenesis.
Main Methods:
- Assessing in vitro angiogenesis in collagen gel with activated PMNs and endothelial cells.
- Measuring Ets-1 expression using ets-1 antisense oligonucleotide.
- Utilizing monoclonal antibodies against ICAM-1 and E-selectin to block specific interactions.
- Investigating angiogenesis stimulated by hydrogen peroxide (H2O2) without PMNs.
Main Results:
- Activated PMNs stimulated both in vitro angiogenesis and Ets-1 expression in endothelial cells.
- Ets-1 antisense oligonucleotide reduced PMN-induced angiogenesis and Ets-1 expression.
- Anti-ICAM-1 antibody reduced PMN-induced Ets-1 expression and angiogenesis, while anti-E-selectin antibody inhibited angiogenesis but not Ets-1 induction.
- Anti-E-selectin antibody inhibited H2O2-stimulated angiogenesis, whereas anti-ICAM-1 did not.
Conclusions:
- Ets-1 is a key mediator in PMN-induced angiogenesis.
- ICAM-1 acts as a signaling receptor on endothelial cells to induce Ets-1 expression.
- E-selectin plays a role in the structural formation of new blood vessels during angiogenesis.