Interplay between Extracellular Matrix and Neutrophils in Diseases

Abstract

The extracellular matrix (ECM) is a highly dynamic and complex network structure, which exists in almost all tissues and is the microenvironment that cells rely on for survival. ECM interacts with cells to regulate diverse functions, including differentiation, proliferation, and migration. Neutrophils are the most abundant immune cells in circulation and play key roles in orchestrating a complex series of events during inflammation. Neutrophils can also mediate ECM remodeling by providing specific matrix-remodeling enzymes (such as neutrophil elastase and metalloproteinases), generating neutrophil extracellular traps, and releasing exosomes. In turn, ECM can remodel the inflammatory microenvironment by regulating the function of neutrophils, which drives disease progression. Both the presence of ECM and the interplay between neutrophils and their extracellular matrices are considered an important and outstanding mechanistic aspect of inflammation. In this review, the importance of ECM will be considered, together with the discussion of recent advances in understanding the underlying mechanisms of the intricate interplay between ECM and neutrophils. A better comprehension of immune cell-matrix reciprocal dependence has exciting implications for the development of new therapeutic options for neutrophil-associated infectious and inflammatory diseases.

Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

“…There is mounting evidence of complex interactions between ECM macromolecules and PMN (reviewed recently by Zhu et al). We now know that the close relationship between ECM and PMNs plays an important role in the progression of various diseases in humans ( 205 ). Recent studies for example demonstrated an important role for ECM in fighting against infectious diseases by mediating an antifungal response of PMNs ( 205 – 207 ).…”

“…We now know that the close relationship between ECM and PMNs plays an important role in the progression of various diseases in humans ( 205 ). Recent studies for example demonstrated an important role for ECM in fighting against infectious diseases by mediating an antifungal response of PMNs ( 205 – 207 ). Moreover, experimental studies have shown that released NETs cleave fibronectin via NE and MMP-9 to further degrade ECM in alveoli, thereby promoting the development of bronchopulmonary dysplasia ( 205 , 208 ).…”

“…Recent studies for example demonstrated an important role for ECM in fighting against infectious diseases by mediating an antifungal response of PMNs ( 205 – 207 ). Moreover, experimental studies have shown that released NETs cleave fibronectin via NE and MMP-9 to further degrade ECM in alveoli, thereby promoting the development of bronchopulmonary dysplasia ( 205 , 208 ). In addition, the interactions of PMN with ECM play a fundamental role in inflammatory conditions of many organs like myocardial injury and pulmonary diseases ( 205 , 209 , 210 ).…”

“…Moreover, experimental studies have shown that released NETs cleave fibronectin via NE and MMP-9 to further degrade ECM in alveoli, thereby promoting the development of bronchopulmonary dysplasia ( 205 , 208 ). In addition, the interactions of PMN with ECM play a fundamental role in inflammatory conditions of many organs like myocardial injury and pulmonary diseases ( 205 , 209 , 210 ). Furthermore, there is a growing evidence that neutrophil invasion into tumor ECM is associated with cancer progression and subsequent metastatic dissemination (for details see 12 Neutrophil Behavior in Cancer Environment and Tumor Tissue ) ( 205 , 211 – 214 ).…”

Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled

“…Through their whole battery of membrane receptors and secretory molecules they communicate with other immune cells to elicit co-operating immune responses for combating the invaders. In addition, they interact with both endothelial and epithelial cells and the extracellular matrix that enable their migration into and through the tissues [ 28 , 29 , 30 ].…”