Cross-Talk among Polymorphonuclear Neutrophils, Immune, and Non-Immune Cells via Released Cytokines, Granule Proteins, Microvesicles, and Neutrophil Extracellular Trap Formation: A Novel Concept of Biology and Pathobiology for Neutrophils

Abstract

Polymorphonuclear neutrophils (PMNs) are traditionally regarded as professional phagocytic and acute inflammatory cells that engulf the microbial pathogens. However, accumulating data have suggested that PMNs are multi-potential cells exhibiting many important biological functions in addition to phagocytosis. These newly found novel activities of PMN include production of different kinds of cytokines/chemokines/growth factors, release of neutrophil extracellular traps (NET)/ectosomes/exosomes and trogocytosis (membrane exchange) with neighboring cells for modulating innate, and adaptive immune responses. Besides, PMNs exhibit potential heterogeneity and plasticity in involving antibody-dependent cellular cytotoxicity (ADCC), cancer immunity, autoimmunity, inflammatory rheumatic diseases, and cardiovascular diseases. Interestingly, PMNs may also play a role in ameliorating inflammatory reaction and wound healing by a subset of PMN myeloid-derived suppressor cells (PMN-MDSC). Furthermore, PMNs can interact with other non-immune cells including platelets, epithelial and endothelial cells to link hemostasis, mucosal inflammation, and atherogenesis. The release of low-density granulocytes (LDG) from bone marrow initiates systemic autoimmune reaction in systemic lupus erythematosus (SLE). In clinical application, identification of certain PMN phenotypes may become prognostic factors for severe traumatic patients. In the present review, we will discuss these newly discovered biological and pathobiological functions of the PMNs.

Neutrophils in chronic inflammatory diseases

“…Future studies targeting neutrophils in chronic inflammation need to consider methods to limit the side effects of treatments. Neutrophils are critical in the acute inflammatory response to infection, and the complete ablation of neutrophils will lead to increased risks of infection, as with the antagonism of CXCR2 in COPD [ 173 , 190 ] and delayed healing [ 199 ]. Possible methods to limit side effects are chronopharmacology and targeted drug delivery with nanoparticles.…”

Exosomes as a New Delivery Vehicle in Inflammatory Bowel Disease

“…In addition, G-MDSC-exo can inhibit CD4 + T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH), which is also related to Arg-1 activity. These findings suggest that G-MDSC-exo alleviate the DSS-induced colitis model mice by inhibiting Th1 cell proliferation and promoting Tregs expansion [94,95].…”

The Multiple Roles of Trogocytosis in Immunity, the Nervous System, and Development

“…Elucidating these mechanisms is becoming a research area of much interest. Two cellular models, the parasitic amoeba E. histolytica [ 22 , 25 ] and neutrophils [ 8 , 98 ], will certainly be used in future research to discover how each process is initiated and regulated. This research will certainly be complicated because we really do not know the exact function of many of the molecules identified to participate in both processes.…”