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Macrophage phagocytosis of wound neutrophils
A J Meszaros1, J S Reichner, J E Albina
1Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, Providence 02903, USA. Adriana_Meszaros@brown.edu
Abstract:
Resolution of acute inflammation is thought to require the recognition and phagocytosis of apoptotic neutrophils (PMN) through receptor-ligand interactions with macrophages (Mphi). This hypothesis was tested in rat wounds by quantifying apoptosis in freshly harvested and aged-in-culture PMN taken from wounds 1-3 days after injury and by using these wound PMN as phagocytic targets for wound, immune-activated peritoneal, and resident peritoneal Mphi. Less than 6% of freshly harvested PMN exhibited characteristics of apoptosis. On aging in culture, day 1 PMN did not undergo apoptosis, whereas 41+/-1 and 29+/-1% of day 2 and 3 PMN, respectively, developed apoptosis, which corresponded to increased ingestion by Mphi. All three Mphi populations engaged different receptor-ligand pairs for the recognition and phagocytosis of PMN. Results indicate the resistance of early wound PMN to age-induced apoptosis, demonstrate wound-Mphi phagocytosis of wound PMN, and identify distinct receptor utilization by wound and other Mphi to ingest wound PMN.
Insights
Inflammation resolution depends on macrophages (Mphi) clearing apoptotic neutrophils (PMN). Early wound PMN resist apoptosis, but later ones are cleared by Mphi using specific receptors.
Area of Science:
- Immunology
- Cell Biology
Background:
- Resolution of acute inflammation involves macrophages (Mphi) phagocytosing apoptotic neutrophils (PMN).
- Receptor-ligand interactions are crucial for this recognition and clearance process.
Purpose of the Study:
- To investigate the apoptosis of neutrophils (PMN) in wound environments.
- To determine the phagocytic capacity of different macrophage (Mphi) populations for wound-derived PMN.
- To identify the specific receptor-ligand interactions involved in PMN phagocytosis by Mphi.
Main Methods:
- Quantifying apoptosis in neutrophils (PMN) harvested from rat wounds at different time points (1-3 days).
- Aging PMN in culture to induce apoptosis.
- Assessing phagocytosis of these PMN by wound-associated Mphi, immune-activated peritoneal Mphi, and resident peritoneal Mphi.
- Analyzing receptor-ligand pairs utilized during phagocytosis.
Main Results:
- Less than 6% of freshly harvested wound neutrophils (PMN) showed apoptosis.
- Neutrophils (PMN) from day 2 and day 3 wounds exhibited significant apoptosis (41% and 29%, respectively) upon aging in culture.
- All tested macrophage (Mphi) populations (wound, immune-activated peritoneal, resident peritoneal) phagocytosed wound PMN.
- Distinct receptor-ligand pairs were utilized by different Mphi populations for PMN ingestion.
Conclusions:
- Early wound neutrophils (PMN) demonstrate resistance to age-induced apoptosis.
- Macrophages (Mphi) within the wound environment effectively phagocytose wound-derived neutrophils (PMN).
- Macrophage (Mphi) recognition and phagocytosis of neutrophils (PMN) involve specific and varied receptor-ligand interactions depending on Mphi origin.