Table 3.

Characteristics of models of knockouts of neutrophil key enzymes.

Mutant	Gene name	Phenotype or limitations	References	Pharmacological inhibitor
MPO−/−	Myeloperoxidase	▪ Increased ROS production by neutrophils ▪ Impaired PMA-induced NETosis ▪ Normal neutrophil counts in diverse tissues tested ▪ Expressed by other cell types (such as monocytes, macrophages, peritoneal B lymphocytes)	(158–162)	4-Aminobenzoichydrazide
NE−/−	Elane	▪ Impaired neutrophil functions (NETosis, pro-inflammatory cytokines release, phagocytosis and transmigration) ▪ Normal circulating leukocyte counts	(159, 163–165)	Sivelestat
Cathepsin G−/−	Cathepsin G	▪ Decreased production of mast cell protease-2. ▪ Normal hematopoietic population counts in diverse tissues tested ▪ Expressed by other cell types (such as splenic dendritic cells and microglia).	(166)	β-keto-phosphonic acid
PAD4−/−	Protein arginine deiminase 4	▪ Increased bone marrow hematopoietic multipotent progenitor numbers ▪ Normal neutrophil morphology and differentiation ▪ Normal circulating neutrophil counts ▪ Expressed by other cell types (such as circulating eosinophils and monocytes) ▪ Impaired NETosis	(167–170)	Cl-Amidine
Ncf1*/*	Neutrophil cytosolic factor 1	▪ Development of spontaneous chronic severe arthritis postpartum ▪ Impaired ROS production by neutrophils and macrophages ▪ Disrupted T cell functions ▪ Impaired NETosis	(171–175)
Proteinase 3−/−	Proteinase 3	▪ Increased bone marrow hematopoietic stem progenitor numbers	(176)
Lactoferrin−/−	Lactoferrin	▪ Normal neutrophil morphology and differentiation ▪ Normal neutrophil functions (phagocytosis, granule mobilization) although defects in PMA-induced oxidative burst ▪ Decrease in circulating lymphocyte counts but increase in circulating neutrophil and eosinophil numbers ▪ Also expressed in monocytes, macrophages and subpopulations of dendritic cells	(177–179)