title: Differential activation of alveolar, pulmonary arterial, and systemic arterial neutrophils demonstrates the existence of distinct neutrophil subpopulations in experimental sepsis.
abstract: Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased beta 2 integrin expression and enhanced superoxide radical (O2-) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O2- and mediate lung injury. In this study we compared alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O2- generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O2- was reduced compared to SA blood PMNs O2- at 5 h, (AIV 5 h 23.6 +/- 3 vs. SA 0 h 34.3 +/- 5, p < .05). SA PMNs O2- generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 +/- 2.5 vs. SA 5 h 16.9 +/- 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 +/- 6 vs. SA PMNs 5 h 51 +/- 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O2- generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Medical College of Virginia-Virginia Commonwealth University, Richmond 23298-0519, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Windsor
authors.forename: P D
authors.initials: PD
authors.lastname: Carey
authors.forename: H J
authors.initials: HJ
authors.lastname: Sugerman
authors.forename: P G
authors.initials: PG
authors.lastname: Mullen
authors.forename: C J
authors.initials: CJ
authors.lastname: Walsh
authors.forename: B J
authors.initials: BJ
authors.lastname: Fisher
authors.forename: C R
authors.initials: CR
authors.lastname: Blocher
authors.forename: A A
authors.initials: AA
authors.lastname: Fowler
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D009504:Neutrophils / Q000145:classification / Q000473:pathology / Q000502:physiology*; D011552:Pseudomonas Infections / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D018805:Sepsis / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D013481:Superoxides / Q000378:metabolism; D013552:Swine
chemical_list: D018821:CD18 Antigens; D013481:Superoxides