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Abstract
Mature neutrophils must be quickly removed from inflammatory sites to prevent tissue damage. Neutrophil removal is thought to be accomplished primarily through caspase-dependent apoptosis, which involves several genes of mitochondrial origin. However, mature neutrophils show reduced gene transcription and mitochondrial numbers. We predicted that neutrophils utilize other cell death mechanisms and investigated programmed cell death in human peripheral blood mononuclear cells (MNCs) and polymorphonuclear cells (PMNCs or neutrophil fractions). Unlike MNCs, PMNCs did not undergo DNA fragmentation and were not TUNEL positive, but expressed LC3-II, an autophagy marker. We also found that during differentiation, autophagy inhibitor 3-MA, and not caspase inhibitor zVAD-fmk, prevented segmentation of the nucleus, indicating that these cells undergo autophagy during maturation. Therefore, human neutrophils may undergo spontaneous autophagic cell death rather than apoptosis, during which autophagy may be essential for both maturation and death.
Highlights
Neutrophils are polymorphonuclear cells (PMNCs) that comprise the first line of defense of the body
Positive dead cells were determined in PMNCs by flow cytometry
DNA fragmentation was evident in mononuclear cells (MNCs) but not in PMNCs (Fig. 1e)
Summary
Neutrophils are polymorphonuclear cells (PMNCs) that comprise the first line of defense of the body. They are key players of the innate immune system with major roles in defending against several bacterial and fungal infections. Neutrophils are identified by their specific segmented nucleus and granules storing antimicrobial molecules. While fully functional neutrophils are essential for defending against infections, they must be efficiently removed from inflamed sites to prevent excessive host tissue damage[1,2]. Neutrophils are produced in the bone marrow and have a high turnover rate. The blood lifespan of neutrophils was reported to be 5.4 days in vivo as compared to ex vivo studies, which estimated their half-life to be 8 h in humans[3]
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