Figure 2.

Cytotoxic functions of neutrophils. Three categories of granules are recognized on the basis of their enzyme content and function, but there is some overlap (12, 258). Primary or azurophilic granules contain the antibacterial enzyme myeloperoxidase (MPO), numerous antimicrobial peptides (e.g., defensins), β-glucuronidase, lysozyme, and serine proteases (e.g., elastase/neutrophil elastase, cathepsin G, and proteinase 3). Secondary or specific granules contain large amounts of lactoferrin, which sequesters free iron to prevent bacterial growth and increases permeability to lysozyme to facilitate breakdown of the bacterial cell wall. Secondary granules also contain matrix metalloproteinases (e.g., MMP8, also known as collagenase). Tertiary granules contain MMP9, also known as gelatinase. Both secondary and tertiary granules contain components of NADPH oxidase, p22^phox and gp91^phox. In addition to the classical granules, neutrophils contain highly mobilizable secretory vesicles that serve as a reservoir primarily for plasma membrane receptors. These include receptors for lipopolysaccharide (CD14), complement (CR1 and CR3/Mac-1), urokinase-type plasminogen activator, immune complexes (FcγRs), and chemoattractants (e.g., to formyl peptides) (10). NADPH oxidase is an electron transport chain that provides electrons from NADPH that reduce O₂ to form superoxide (·O₂⁻), which spontaneously dismutates into various reactive oxygen species such as hydrogen peroxide, singlet oxygen, hydroxyl radicals, and possibly ozone (259). Abbreviations: BPI, bactericidal/permeability-increasing protein; CR, complement receptor; FcγR, Fcγ receptor; iNOS, inducible nitric oxide synthase; Mac-1, macrophage-1 antigen; NET, neutrophil extracellular trap; TLR, Toll-like receptor.