Neutrophils and Immunity: From Bactericidal Action to Being Conquered

Table 1

Mechanism of action of neutrophil antimicrobial proteins/peptide.

Antimicrobial protein/peptide	Direct antimicrobial mechanism	Alternative antimicrobial mechanism	Subcellular localization	Ref.
α-Defensins	Membrane-active; inhibition of DNA, RNA, protein, bacterial cell wall synthesis	Opsonisation of bacteria/ROS formation	Primary granules, NETs	[21]
LL-37	Transmembrane pore-forming	ROS formation	Secondary granules, NETs	[22]
BPI	Hydrolysis of bacterial phospholipids by binding to LPS	Inhibiting cytokine liberation by binding to CD14	Primary granules	[23, 24]
Histones	Membrane-active	NETs formation	Nucleus, NETs	[25]
Lysozyme	Degrades bacterial cell wall	NETs formation	Lysosomes	[5, 26]
PR3	Proteolytic activity; degrading virulence factors	NETs formation	Primary granules/NETs	[27–29]
NE	Proteolytic activity; degrading virulence factors	NETs formation	Primary granules/NETs	[27–29]
CatG	Proteolytic activity	NETs formation; ROS formation	Primary granules/NETs	[28, 29]
NSP4	Trypsin-like activity	Unknown	Primary granules	[30–32]
Azurocidin	Membrane-active	Opsonisation of bacteria	Primary granules	[33]
Lactoferrin	Altering bacterial growth by binding to iron; increase in membrane permeability by binding to the lipid A	Decreasing the release IL-1, IL-2, and TNFα; Suppressing NETs release	Secondary granules/NETs	[34–37]
Calprotectin	Altering bacterial growth by sequestering Mn^2+ and Zn^2+	Inhibition of Mn^2+-dependent bacterial superoxide defenses; NETs formation	Secondary granules	[38, 39]
PTX3	As a soluble pattern recognition receptor in innate immunity	NETs formation	Secondary granules/NETs	[40]
NADPH oxidase	Generation of superoxide anion	NETs formation	Lysosomes	[41]
MPO	Generation of hypochlorous acid	NETs formation	Lysosomes	[18, 42, 43]
Platelets	Activating neutrophils to release NETs	NETs formation	NETs	[44]
NGAL	Inhibit bacteria growth by capturing and depleting siderophores	Acting as a growth and differentiation factor in multiple cell type	Secondary granules	[45, 46]