Figure 1. Neutrophil lifespan and stages of maturation, showing the flux through each compartment and the time in each compartment. The area of each section indicates the number of cells in each compartment. The stepwise increase through the first three compartments represents serial divisions of the cells in these compartments. In the promyelocyte stage, the azurophil granules (red dots) are formed, whereas the specific granules (purple organelles) are formed in the myelocytic stage. Note that no divisions occur after the myelocyte stage. Reproduced with permission from Bainton DF (1980) The cells of inflammation: A general view. In: Weissmann G (ed.) The Cell Biology of Inflammation, vol. 2, pp. 1–25. Amsterdam: Elsevier/North-Holland.

Figure 2. Neutrophil activation through G protein-coupled receptors of the sevenspan supergene family. Most chemotaxin receptors belong to this gene family, being characterized by seven transmembrane-spanning domains. The intracellular loops and C-terminus define the association with different G proteins and, as a consequence, part of the secondary signalling cascades that may become activated upon ligand binding. The activation of cytoplasmic enzymes, such as phospholipases C, D and A₂, and different protein kinases (PK), each with their own substrates and products, leads to several of the effector functions of neutrophils. PC, phosphatidylcholine; PIP₂, phosphoinositol-4,5-bisphosphate.

Figure 3. Neutrophil influx into tissue. Initial interactions among selectin members and their respective carbohydrate receptor structures (sialyl Lewis-X determinants) causes ‘rolling’ of the neutrophils (PMN) over the blood vessel wall (1). E selectin and ICAM-1 are increased in expression on endothelial cells in infectious areas. E selectin binds to sialyl Lewis-X on the neutrophils and ICAM-1 to the ₂-integrin CR3 on the neutrophils. This last process causes a tight binding to and spreading of the neutrophils on the vessel wall (2). Platelet-activating factor (PAF) and interleukin 8 (IL-8), produced by endothelial cells (EC) in infectious areas, then induce the neutrophils to squeeze between the endothelial cells into the tissues. Neutrophils in the middle of the bloodstream continue to circulate (3).

Figure 4. Schematic representation of the three selectin members: L selectin (CD62L) on leucocytes; E selectin (CD62E) on activated endothelium; P selectin on activated endothelium and platelets. The number of sequence consensus repeats (SCR) differs among the selectin members. The EGF-like domain represents the ligand-binding site. This domain is called lectin-like because of its ability to recognize a particular carbohydrate determinant, i.e. sialyl Lewis-X (sLe^x). EGF, epidermal growth factor.

Figure 5. The integrin supergene family. One chain may associate with any one of various chains. The ₁-integrins recognize extracellular matrix components. Only ₄₁ (VLA-4) is also able to bind to a cellular ligand, VCAM-1, predominantly expressed on endothelial cells. Neutrophils predominantly express the ₂-integrins, CD11b/CD18 (CR3) in particular, at very high levels. This receptor is used as adhesion receptor through binding to ICAM-1 and several different extracellular matrix (ECM) proteins, as well as an opsonin receptor for inactivated C3b (C3bi) fragments deposited on opsonized microorganisms.

Figure 6. Recognition, uptake and killing of microorganisms by neutrophils. Opsonized microorganisms bind with Fc regions of IgG antibodies to Fc receptors, and with C3b/C3bi fragments to complement receptors CR1 and CR3 on the surface of the neutrophils. As a result, the microorganisms are engulfed by the neutrophils and taken up into an intracellular phagosome. Neutrophil granules fuse with the phagosome membrane and deposit their contents into the phagosome. A membrane-bound oxidase is activated and starts to generate superoxide ( O₂^–), also into the phagosome. The superoxide is spontaneously converted into hydrogen peroxide ( H₂O₂), which reacts with myeloperoxide (MPO) released from the granules to yield additional toxic oxygen compounds. BPI, bactericidal permeability-increasing protein.