Interplay between Extracellular Matrix and Neutrophils in Diseases

Table 1

Effects of neutrophil- released factors on extracellular matrix function.

Neutrophil-released factors	Effects on ECM	Diseases	References
NE	Degradation of ECM components (elastin, collagen, fibronectin, and proteoglycan)	COPD, IBD	[69, 33]
	Destroys the tight junctions between cells and increases tissue permeability	ALI, ARDS, lung cancer, etc.	[32, 71, 72]
	Protease-antiprotease imbalance
MMPs	Upregulation of MMP-8 and MMP-9 leads to the degradation of lung structural proteins (collagen and elastin)	TB	[35, 36]
	MMP-9·NGAL complexes protect and prolong the proteolytic activity of MMP-9	OA	[73]
	Upregulation of MMP-1, MMP-8, and MMP-9	Tumor metastasis	[74, 75]
	Degrade the fibrous caps and collagen, which promote plaque instability and rupture	Atherosclerosis	[76]
Cathepsin G	Cleavage of endothelial cadherin and fibronectin		[43]
	Activation of MMPs, which increases TNF-α and IL-8	Atherosclerosis	[44]
	Induce E-cadherin/catenin complex formation and improve the cell adhesion strength of E-cadherin-mediated MCF-7 cells	Breast cancer	[48]
NETs	Bind to the extracellular laminin, trigger integrin and FAK/ERK/MLCK/YAP signaling, and awaken dormant cancer cells	Lung cancer	[26]
	NE and MMP-9 cleave ECM proteins	BPD	[62]
	NE degrades cartilage matrix	RA	[61]
Exosomes	Degrade ECM by binding to NE and integrin Mac-1	COPD	[69]
	Resist the inhibitory effect of α1-antitrypsin	BPD; Asthma	[68]

Note. ECM: extracellular matrix; BM: basement membrane; NE: neutrophil elastase; MMPs: matrix metalloproteinases; NETs: neutrophil extracellular traps; TNF-α: tumor necrosis factor alpha; IL-8: interleukin-8; MMP-9: matrix metalloproteinase-9; NGAL: neutrophil gelatinase-associated lipocalin; COPD: chronic obstructive pulmonary disease; IBD: inflammatory bowel disease; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; BPD: bronchopulmonary dysplasia; RA: rheumatoid arthritis; OA: osteoarthritis; TB: tuberculosis.