An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration

Abstract

Despite considerable recent progress in defining neutrophil functions and behaviors in tissue repair, much remains to be determined with regards to its overall role in the tissue integration of biomaterials. This article provides an overview of the neutrophil's numerous, important roles in both inflammation and resolution, and subsequently, their role in biomaterial integration. Neutrophils function in three primary capacities: generation of oxidative bursts, release of granules and formation of neutrophil extracellular traps (NETs); these combined functions enable neutrophil involvement in inflammation, macrophage recruitment, M2 macrophage differentiation, resolution of inflammation, angiogenesis, tumor formation and immune system activation. Neutrophils exhibit great flexibility to adjust to the prevalent microenvironmental conditions in the tissue; thus, the biomaterial composition and fabrication will potentially influence neutrophil behavior following confrontation. This review serves to highlight the neutrophil's plasticity, reiterating that neutrophils are not just simple suicidal killers, but the true maestros of resolution and regeneration.

Keywords: NETosis; host response; inflammation; neutrophil; tissue engineering; tissue regeneration.

Figure 1.

Neutrophil crosstalk with immune and humoral cells and relevant chemical signals that influence and compose the inflammatory response and pathway to resolution via the neutrophil.

Figure 2.

Schematic of the neutrophil undergoing NETosis.

Figure 3.

Scanning electron micrograph (scale bar represents 1 µm) of NETs trapping/entangling pathogens [22]. Reprinted with permission from original publisher. © 2012 Brinkmann and Zychlinksy. Journal of Cell Biology. 198:773-783,doi:10.1083/jcb.201203170.

Figure 4.

Schematic relays the distinct differences between N1 (anti-tumoral) and N2 (pro-tumoral) neutrophils.

Figure 5.

Representative fluorescent images of freshly isolated neutrophils seeded onto polydioxanone electrospun templates at 3 hrs. Top panel a is a large fiber diameter (1.9 ± 1 µm) template while bottom panel B shows a small fiber diameter (0.3 ± 0.1 µm) template eliciting a greater amount of NET extrusion. The stains utilized are DAPI (blue) for nuclei and SYTOX green (green) for extracellular chromatin, or NETs. For both images, magnification is 40× and scale bar is 50 µm.