CD18 dependency of transendothelial neutrophil migration differs during acute pulmonary inflammation

Neutrophil extravasation during inflammation can occur either by a mechanis m that requires the neutrophil integrin complex, CD18, or by an alternative CD18-independent route. Which of the two pathways is used has been shown t o depend on the site and nature of the inflammatory insult. More recent evi dence suggests that selection may also depend on whether inflammation is ch ronic or acute, but why this is the case remains unknown. Using an in vitro model that supports both migratory mechanisms, we examined the CD18 depend ency of migration of neutrophils isolated from patients with either chronic or acute pulmonary infection. Chronic neutrophils were found to behave lik e normal neutrophils by migrating to IL-8 and leukotriene B-4 using the CD1 8-independent pathway, but to the bacterial product, FMLP, using the CD18-d ependent route. In contrast, migration of acute neutrophils to all of these stimuli was CD18 dependent. Normal neutrophils could be manipulated to res emble acute neutrophils by exposing them to FMLP before migration, which re sulted in a "switch" from the CD18-independent to -dependent mechanism duri ng migration to IL-8 or leukotriene B-4. Although treatment of normal neutr ophils with FMLP caused selective down-regulation of the IL-8 receptor, CXC R2, and acute neutrophils were found to have less CXCR2 than normal, a func tional relationship between decreased CXCR2 and selection of CD18-dependent migration was not demonstrated. Results indicate that selection of the CD1 8-dependent or -independent migration mechanism can be controlled by the ne utrophil and suggest that the altered CD18 requirements of acute neutrophil s may be due to priming in the circulation during acute infection.