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Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development
1NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea.
Cell Death and Differentiation
|June 27, 2009
Summary
Macrophages use Ninjurin1 (Ninj1) to trigger cell death during developmental tissue remodeling. Blocking Ninj1 delays this process, revealing its crucial role in vascular regression.
Area of Science:
- Developmental Biology
- Immunology
- Cell Biology
Background:
- Macrophages play key roles in tissue regression, including phagocytosis and direct induction of apoptosis.
- In the hyaloid vascular system (HVS), macrophages induce vascular endothelial cell (VEC) apoptosis via Wnt and angiopoietin (Ang) pathways.
- The precise mechanisms of macrophage activation and VEC interaction during HVS regression are not fully understood.
Purpose of the Study:
- To investigate the role of Ninjurin1 (Ninj1) in macrophage-mediated apoptosis during HVS regression.
- To elucidate the molecular mechanisms by which Ninj1-expressing macrophages interact with and induce apoptosis in VECs.
Main Methods:
- Temporal analysis of Ninjurin1 expression in macrophages during HVS regression.
- In vivo studies using systemic neutralization with an anti-Ninj1 antibody.
- Assessment of macrophage adhesion properties.
- Analysis of Wnt7b expression in macrophages and angiopoietin levels in pericytes.
Main Results:
- Ninjurin1 expression was upregulated in macrophages during HVS regression, correlating with close interactions with hyaloid VECs.
- Systemic blockade of Ninj1 significantly delayed HVS regression in vivo.
- Ninj1 enhanced macrophage cell-cell and cell-matrix adhesion.
- Ninj1 stimulated Wnt7b expression in macrophages and altered angiopoietin profiles in pericytes, promoting VEC death.
Conclusions:
- Macrophages express Ninjurin1 to facilitate developmental tissue regression, specifically HVS regression, through enhanced cell-cell interactions and modulation of signaling pathways.
- Ninj1 acts by increasing macrophage adhesion, stimulating Wnt7b, and altering pericyte angiopoietin expression, ultimately inducing VEC apoptosis.
- Ninj1 represents a potential therapeutic target for modulating developmental regression processes mediated by macrophages in various biological contexts.
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