FIGURE 1.

Summary of different neutrophil functions. (A) Effective migration is a prerequisite to any subsequent function executed by neutrophils. Neutrophils in circulation rely on various interactions with the endothelium. These include (1) loose binding of carbohydrate ligands on neutrophils (such as sialyl‐Lewis^X and P‐selectin glycoprotein ligand 1) to selectins (E‐selectin and P‐selectin, respectively) on activated endothelium, which induce rolling of neutrophils along endothelial cells; (2) sensing of chemokines (including CXCL8) by chemokine receptors on neutrophils (e.g., CXCR2), which in turn activates the integrins lymphocyte function‐associated antigen 1 (LFA‐1, consisting of CD11a and CD18) and complement receptor 3 (CR3; made of CD11b and CD18) on neutrophils; (3) the activated integrins LFA‐1 and CR3 on neutrophils strongly adhere to intercellular adhesion molecule 1 (ICAM‐1) and ICAM‐2 on activated endothelial cells, thus arresting neutrophils and allowing their transmigration through the endothelium (also called extravasation) into the tissue. Neutrophil migration, facilitated by adhesion molecules and chemotactic sensors for recruitment, is absolutely crucial, as illustrated by immunodeficiencies due to leukocyte adhesion deficiency (please see Table 1) that can lead to life‐threatening conditions. (B) Neutrophils are excellent at direct combat and feature a wide repertoire of effector functions, such as phagocytosis, degranulation of primary, secondary, tertiary, and secretory vesicles, production of reactive oxygen species (ROS; such as superoxide [O₂ ⁻], hydrogen peroxide [H₂O₂], and hypochloride [HOCl]), and release of neutrophil extracellular traps (NETs) consisting of either nuclear or mitochondrial DNA. (C) Their rapid mobilization to affected tissues allows neutrophils to guide the recruitment and activity of other cells involved in the inflammatory process, such as dendritic cells (DCs), monocytes (Mono), macrophages (Macs), CD4⁺ T helper cells, and CD8⁺ cytotoxic T cells by releasing or leaving “trails” of chemokines (such as CXCL12 and CCL3) and cytokines (e.g., epidermal growth factor [EGF]). (D) Whereas the importance of neutrophils for immune defense is irrefutable, recent evidence suggests they are also involved in tissue‐specific non‐immune processes. Neutrophils extravasate to various tissues at steady state and engage in non‐canonical functions, such as angiogenesis, tissue repair, and wound healing.