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Development and Identification of a Novel Subpopulation of Human Neutrophil-derived Giant Phagocytes In Vitro
Published on: January 25, 2017
Macrophage-induced neutrophil apoptosis
A J Meszaros1, J S Reichner, J E Albina
1Department of Surgery, Rhode Island Hospital, Brown University School of Medicine, Providence, RI 02903, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|June 22, 2000
Summary
Wound macrophages actively induce polymorphonuclear neutrophil (PMN) apoptosis through direct cell contact. This process requires integrin-ligand interactions and membrane-bound TNF-alpha, crucial for inflammation resolution.
Area of Science:
- Immunology
- Cell Biology
- Wound Healing Research
Background:
- Macrophages (Mphi) are key in resolving inflammation by clearing apoptotic cells.
- Polymorphonuclear neutrophils (PMN) are early responders to inflammation.
- The precise mechanisms by which macrophages induce PMN apoptosis are under investigation.
Purpose of the Study:
- To investigate the role of wound-associated macrophages in actively inducing PMN apoptosis.
- To elucidate the molecular mechanisms involved in Mphi-mediated PMN apoptosis.
Main Methods:
- Coculture of rat wound cells and purified macrophages with PMN-rich populations.
- Inhibition studies using peptide inhibitors and antibodies against specific molecules (e.g., integrins, TNF-alpha).
- Transfection of K562 cells to express specific proteins (integrin, membrane-bound TNF-alpha) for mechanistic studies.
Main Results:
- Wound macrophages significantly increased PMN apoptosis (>3-fold) in coculture experiments.
- Mphi-induced apoptosis required direct cell-to-cell contact and was not mediated by soluble factors.
- Inhibition studies implicated integrin-ligand interactions and membrane-bound TNF-alpha in the apoptotic process.
- Transfected cells demonstrated that combined expression of integrin and membrane-bound TNF-alpha was necessary and sufficient to induce PMN apoptosis.
Conclusions:
- Wound macrophages possess a constitutive mechanism to induce PMN apoptosis.
- This mechanism relies on intercellular binding via integrin-ligand interactions and membrane-bound TNF-alpha.
- These findings highlight a novel pathway for inflammation resolution mediated by macrophages.
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