In addition to ingesting small microorganisms such as bacteria by phagocytosis, neutrophils and eosinophils can assist in the elimination of larger invaders by trapping them within webs called neutrophil extracellular traps or NETs (Figure 1). The strands for these NETs are composed of polynucleotide strands generated by the dispersal, or decondensation, of a neutrophil’s chromosomal DNA. This process involves rupture of the nuclear membrane and the disruption of the favorable charge–charge interactions that normally stabilize chromatin. Dissolution of histone-polynucleotide complexes is promoted by the enzyme peptidylarginine deiminase, which catalyzes the deimination of the strongly basic side chains of arginine residues to form neutral citrulline residues (Figure 2). Some chromatin proteins do remain associated with the DNA, forming cross-links between the polynucleotide strands. Granule membranes also rupture at this time, releasing their contents into the cytoplasm where they can bind to the decondensing polynucleotide strands, decorating the DNA with granule-derived proteases, antimicrobial peptides, and other factors. Eventually, the neutrophils lyse, unleashing their NETs on invading parasites in order to immobilize them and hinder their spread.
Fig1. Trapping parasites using NETs. The figure depicts the basic stages in the formation and deployment of a DNA-based web by a neutrophil or eosinophil to trap a parasitic microorganism. (A) Resting neutrophil. The multilobed nucleus is shown in hatched purple, intracellular granules in green, and granule enzymes and cytotoxins as orange circles and yellow triangles. (B) On stimulation, the membranes encasing the nucleus and granules rupture, releasing enzymes, cytotoxins, and strands of DNA (purple) from decondensing chromosomes.(C)The DNA strands form a mesh that fills the interior of the cell to which some granule-derived proteins adhere. (D)The neutrophil lyses, releasing its DNA-protein web, which entraps the parasite (orange) against surface of the epithelium (hatched).
Fig2. Citrullination. The enzyme peptidyl arginine deiminase displaces one of the imino groups (red) on the side chain of arginine by an oxygen atom (blue) derived from water. The net result is to replace a positive charge provided by the protonated arginine side chain by an amide, which is neutral.
