Table 1.

Neutrophil granules and their factors of interest. Chemokine production and secretion play a significant role in cellular migration, wound healing, hematopoiesis, angiogenesis, and tumor metastasis, all critical to the neutrophil’s function [4]

Granule	Factor of Interest	Function	Role in Immune System Guided In Situ Regeneration
Primary Azurophilic granules	NE (serine protease)	Degrades collagen-IV and elastin within ECM [15]	Positive feedback loop for the inflammatory response [27]
		Targets bacteria’s virulent vectors [28]
		Up-regulates expression of TLR 4 expression in monocytes [27]
		Tissue remodeling [4]
	Defensins	Disrupts cytoplasmic membrane of microbes and induces migration of naïve T cells and immature DCs [29]	Active adaptive immunity to combat infection [D. 29]
		Induces chemotaxis of CD4+ and CD8+ cells (30)	Links innate and adaptive immunity through the neutrophil (30)
	MPO (peroxidase)	Production of antimicrobial oxidants [31]	Facilitates NET release [32]
		Enables translocation of NE to the nucleus [32]
		Reacts with H2O2 which increases toxic potential by inducing the formation of hypochlorous acid (chlorination products, tyrosine radicals and reactive nitrogen intermediates) [15, 30]
	Lysozyme	Cleaves peptidoglycan polymers of bacterial cell walls [30]
	Bactericidal/permeability increasing protein (BPI)	Kills gram-negative bacteria at non-molar concentrations by binding to negatively charged residues of LPS which promotes bacterial attachment and allows for phagocytosis [15, 30]
		Endotoxin-neutralizing proteins [15]
	Proteinase 3	Induces activation of epithelial cells, endothelial cells, macrophages, lymphocytes, and platelets [30]
	Cathepsin G (serine protease)	Kills pathogens [15]	Tissue remodeling [15]
		Degrades ECM proteins [15]
		Induces activation of epithelial cells, endothelial cells, macrophages, lymphocytes, and platelets [30]
	Azurocidin	Induces chemotaxis of CD4+ and CD8+ cells [30]
		Antimicrobial activity [15]
	Vitronectin	Promotes neutrophil adhesion and migration through interaction with integrins [33]
		Inhibits apoptosis of neutrophils [33]
Secondary Specific granules	Lactoferrin	Wide range of microbicidal activity against pathogens (15)
		N-terminal amphipathic α-helical region [30]
		Iron-binding proteins and impairs bacterial growth (gram − and +) by sequestration of iron [30]
	Collagenase (MMP-1 and MMP-8)	Degrades major structural components of ECM [30]	MMP-8 has been deemed a tumor-protective protein, possibly to be an anti-tumor agent against MMP-9 [34]
		Responsible for loss of vascular basement membranes during neutrophil extravasation and migration [30]
	M-Ficolin	Interacts with microbial entities and activates the lectin pathway of the complement cascade [4]
	Neutrophil gelatinase associated lipocalin	Antibacterial activity through sequestration of ferric-siderophore complexes [30]	Is produced commonly by neutrophils in normal, inflamed, and neotissue [30]
		Strongest iron chelators known [35]	Plays a role in iron-depleting strategy affecting bacterial growth [30]
	Human cathelicidin antimicrobial protein-18 (hCAP-18)	Antimicrobial peptide (−/+), induces chemotaxis of neutrophils, T cells and monocytes when isolated from cathelin propiece [30]	During wound healing, insulin-like growth factor 1 (IGF-1) induces secretion of hCAP-18 in keratinocytes and hCAP-18 is constitutively expressed in monocytes and lymphocytes elsewhere [30]
	Flavocytochrome b558	Terminal electron carrier of the assembled respiratory burst oxidase [30]
	Lysozyme	Binds LPS and reduces cytokine production [30]
		Bactericidal activity against non-pathogenic bacteria [30]
	Secretory leukocyte protease inhibitor (SLPI)	Neutralizes elastase and cathepsin G., activates MMPs, inhibits macrophage MMPs and tumorigenesis; absence of SLPI associated with reduced ECM production and poor healing [36]
	Pentraxin 3	Antimicrobial properties [37]	Stimulated by LPS, neutrophil activation etc. and can continue to be released in response to inflammatory cytokines [37]
		Microbial recognition [4]
	NADPH oxidase	Aids respiratory burst upon neutrophil activation and subsequent ROS production/release [15]
	Leukolysin (MMP-25) (10% of total leukolysin present in cell)	Degrades major structural components of ECM [30]
		Loss of vascular basement membranes during neutrophil extravasation and migration [30]
Tertiary Gelatinase granules	Gelatinases A and B (MMP- 2 and MMP-9)	Degrades major structural components of ECM [30]	Inhibition of gelatinases results in suppressed neutrophil attachment and migration [38]
		Loss of vascular basement membranes during neutrophil extravasation and migration [30]	Excessive amounts of MMP-9, potent stimulator of angiogenesis, seen in N2 neutrophils plays a role in invasive tumor growth [34]
		Tissue remodeling [4]
	Flavocytochrome b558	Terminal electron carrier of the assembled respiratory burst oxidase [30]
	Arginase-1	Inhibits T cell proliferation [39]	Lack of Arginase-1 is associated with reduced healing, inflammation, increased collagen deposition and mast cell migration [40]
	Leukolysin (MMP-25) (40% of total leukolysin present in cell)	Degrades major structural components of ECM [30]	Allows for neutrophil migration and matrix reprogramming
		Loss of vascular basement membranes during neutrophil extravasation and migration [30]
Secretory Vesicles	β2-integrin CD11b/CD18 (Mac-1, CR3)	Promotes apoptosis of neutrophils [41]	When mobilized, there is a shedding of L-selectin from neutrophil’s surface which allows for neutrophil firm contact with the vascular endothelium in vivo [30]
			Increased apoptosis of neutrophils can lead to resolution of inflammation [41]
	Formylated bacterial peptides (fMLP-receptors)	G-PCR	In LPS stimulated neutrophils, fMLP can inhibit TNF-α providing an anti-inflammatory effect on monocytes and macrophages [42]
		Pro-inflammatory agent [42]