Neutrophil trafficking in the lung. Neutrophils (polymorphonuclear leukocytes [PMNs], colored blue) enter a pulmonary capillary (left). Because of the small diameter of the capillary, neutrophils must deform, which increases transit time ('margination') even under resting conditions (inset A: margination). In venules, adhesion molecule (AM)-dependent rolling can occur. In response to an inflammatory stimulus (red arrow), neutrophils adhere to the capillary endothelium (inset B: sequestration). AMs and chemokines (not shown) might be involved in this process. Alveolar macrophages and type II pneumocytes produce CXC chemokines, which attract neutrophils to migrate through the endothelium (inset C1: transendothelial migration), interstitial space, and epithelium (inset C2: transepithelial migration) to reach the alveolar space. The requirement of AMs for the different steps is dependent on the stimulus and the used model (see text for details). Arrows indicate directions of flow, and dashed lines indicate endothelial and epithelial basement membrane.