title: CD18 dependency of transendothelial neutrophil migration differs during acute pulmonary inflammation.
abstract: Neutrophil extravasation during inflammation can occur either by a mechanism that requires the neutrophil integrin complex, CD18, or by an alternative CD18-independent route. Which of the two pathways is used has been shown to depend on the site and nature of the inflammatory insult. More recent evidence suggests that selection may also depend on whether inflammation is chronic or acute, but why this is the case remains unknown. Using an in vitro model that supports both migratory mechanisms, we examined the CD18 dependency of migration of neutrophils isolated from patients with either chronic or acute pulmonary infection. Chronic neutrophils were found to behave like normal neutrophils by migrating to IL-8 and leukotriene B(4) using the CD18-independent pathway, but to the bacterial product, FMLP, using the CD18-dependent route. In contrast, migration of acute neutrophils to all of these stimuli was CD18 dependent. Normal neutrophils could be manipulated to resemble acute neutrophils by exposing them to FMLP before migration, which resulted in a "switch" from the CD18-independent to -dependent mechanism during migration to IL-8 or leukotriene B(4). Although treatment of normal neutrophils with FMLP caused selective down-regulation of the IL-8 receptor, CXCR2, and acute neutrophils were found to have less CXCR2 than normal, a functional relationship between decreased CXCR2 and selection of CD18-dependent migration was not demonstrated. Results indicate that selection of the CD18-dependent or -independent migration mechanism can be controlled by the neutrophil and suggest that the altered CD18 requirements of acute neutrophils may be due to priming in the circulation during acute infection.
authors.affiliation: Department of Medicine and Therapeutics, University College Dublin, Dublin, Ireland. Jill.Mackarel@ucd.ie
authors.forename: A J
authors.initials: AJ
authors.lastname: Mackarel
authors.forename: K J
authors.initials: KJ
authors.lastname: Russell
authors.forename: C M
authors.initials: CM
authors.lastname: Ryan
authors.forename: S J
authors.initials: SJ
authors.lastname: Hislip
authors.forename: J C
authors.initials: JC
authors.lastname: Rendall
authors.forename: M X
authors.initials: MX
authors.lastname: FitzGerald
authors.forename: C M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018821:CD18 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D023062:Receptors, Interleukin-8A / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism
chemical_list: D018821:CD18 Antigens; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D009240:N-Formylmethionine Leucyl-Phenylalanine