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A novel effect of polymorphonuclear leukocytes in the facilitation of angiogenesis
M Yasuda1, S Shimizu, S Tokuyama
1Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Abstract:
The purpose of this study was to examine whether the adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells and/or reactive oxygen species (ROS) released from PMNs are responsible for inducing angiogenesis. Angiogenesis was assessed by tube formation using endothelial cells obtained from bovine thoracic aorta (BAECs) grown on a layer of collagen type I. Addition of PMNs to BAECs weakly induced angiogenesis. The angiogenesis induced by PMNs alone was further enhanced by treatment of the PMNs with N-formyl-methionyl-leucyl-phenylalanine (FMLP), a selective activator of PMN. The involvement of PMN adhesion to BAECs via adhesion molecules in angiogenesis was investigated by using monoclonal antibodies against E-selectin and intercellular adhesion molecule-1 (ICAM-1). These antibodies blocked both the PMN adhesion to BAECs and the enhancement of angiogenesis induced by FMLP-treated PMNs. Furthermore, the enhancement of angiogenesis by FMLP-treated PMNs was blocked by catalase, a scavenging enzyme of H2O2, but not by superoxide dismutase (SOD). These results suggest that PMNs induce angiogenesis in vitro, and that the mechanism of stimulation of angiogenesis by PMNs may involve the adherence of PMNs to endothelial cells via E-selectin and ICAM-1, and H2O2, but not superoxide. Thus, activated PMNs in pathological states may not only induce tissue injury, but may also function as regulators of angiogenesis.
Insights
Polymorphonuclear leukocytes (PMNs) promote angiogenesis, the formation of new blood vessels. Their adhesion to endothelial cells and hydrogen peroxide release are key mechanisms, suggesting PMNs regulate blood vessel growth in disease.
Area of Science:
- Cell Biology
- Immunology
- Vascular Biology
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for various physiological and pathological processes.
- Polymorphonuclear leukocytes (PMNs) are immune cells involved in inflammation and tissue repair.
- The role of PMNs and their secreted factors in regulating angiogenesis remains incompletely understood.
Purpose of the Study:
- To investigate whether PMN adhesion to endothelial cells and/or reactive oxygen species (ROS) produced by PMNs induce angiogenesis.
- To elucidate the specific molecular mechanisms, including adhesion molecules and ROS, involved in PMN-mediated angiogenesis.
Main Methods:
- Assessed angiogenesis using tube formation assays with bovine aortic endothelial cells (BAECs).
- Utilized N-formyl-methionyl-leucyl-phenylalanine (FMLP) to activate PMNs.
- Employed monoclonal antibodies against E-selectin and intercellular adhesion molecule-1 (ICAM-1) to block adhesion molecules.
- Used catalase and superoxide dismutase (SOD) to scavenge specific reactive oxygen species.
Main Results:
- PMNs alone weakly induced angiogenesis (tube formation) in BAECs.
- FMLP-activated PMNs significantly enhanced angiogenesis.
- Antibodies against E-selectin and ICAM-1 inhibited PMN adhesion and FMLP-induced angiogenesis.
- Catalase blocked the enhancement of angiogenesis by activated PMNs, while SOD did not.
Conclusions:
- PMNs can induce angiogenesis in vitro, with activation significantly enhancing this effect.
- PMN adhesion to endothelial cells via E-selectin and ICAM-1 is critical for this pro-angiogenic activity.
- Hydrogen peroxide (H2O2), but not superoxide, released by activated PMNs mediates the pro-angiogenic effect.
- Activated PMNs may act as regulators of angiogenesis in pathological conditions, potentially contributing to tissue injury and repair.