PMNs on Their Way to Lung-Sequestration, Adhesion, Migration, Activation, and Tissue Injury. First, in response to inflammatory mediators, PMNs migrate to the pulmonary capillaries in preparation for extravasation ( Figure 1 ). Initial changes in the cyto-skeleton prevent PMNs from deforming, making it less likely for them to pass through the pulmonary capillaries (51) . In this regard, activated PMNs from ARDS patients appeared even more rigid than those from septic patients (52) . Second, emigration of PMNs and passage through the endothelium can be regulated through adhesion molecules (51) . While their initial sequestration appears to be independent from adhesion molecules, the durability of this process could rely on them. Thus, while L-selectin-deficient mice showed a normal pool of marginated PMNs and cleavage of L-selectin from the PMN surface did not alter this margination (53, 54) , L-selectin deficient mice exhibited only a very short and transient leukopenia in response to complement activation (53, 55) . PMNs can adhere to endothelial cells using CD11/CD18 interacting with intercellular adhesion molecule-1 (ICAM-1) on the endothelial side. Thus, PMN emigration in response to Escherichia coli (E.coli), E.coli lipopolysaccharide, Pseudomonas aeruginosa, immunoglobulin (Ig) G immune complexes, and IL-1 was mediated through CD11/CD18, but this did not appear to be the case in response to Streptococcus pneumoniae, Group B Streptococcus, Staphylococcus aureus, hyperoxia, or C5a (56) . Even in CD11/CD18-dependent migration, blocking of CD18 reduced PMN emigration only by 60% to 80%, suggesting that other redundant mechanisms mediated these effects (56) . Cytokines and chemokines such as IL-8 also have been shown to be involved in increasing β2-integrin avidity (57) . It is important to understand that activation of PMNs is associated closely with the endothelial interaction mediated by the adhesion molecules (57, 58) . Rolling PMNs might well integrate the sum total of inputs received while scanning the endothelium. If an activation threshold is reached, β2-integrins switch to the high-affinity conformation, redistribute on the cell surface, and trigger arrest and adhesion (59, 60) . However, integrins also are involved in PMN migra-tion, phagocytosis, respiratory burst, and even cytokine production (57, 61, 62) .