title: Zymosan-activated plasma causes prolonged decreases in PMN superoxide release in sheep.
abstract: It is well established that activation of neutrophils within the pulmonary circulation produces acute lung injury in which adherence of neutrophils to endothelial cells is an obligatory step in the mechanism of injury. The effects of in vivo activation of neutrophils on the in vitro responses of these cells to stimulation have not been determined, although such information may be important in understanding how different etiological factors may interact to produce infection or acute respiratory failure. By using an assay to sequentially measure superoxide anion (O2-) release from adherent neutrophils stimulated with phorbol myristate acetate (PMA), we measured the in vitro activation response of peripheral blood neutrophils isolated before and 24 h after infusion of zymosan-activated plasma (ZAP; or untreated plasma as a control), air bubbles, or PMA in awake, instrumented sheep. Each of the three inflammatory agents produced an increase in lung microvascular permeability characteristic of acute lung injury; control plasma did not. For the in vivo ZAP experiments, stimulated O2- release in vitro by using PMA was approximately 50% lower (P less than 0.05) for neutrophils isolated 24 h after the in vivo infusion (4.3 +/- 0.8 nmol/500,000 cells) than before (8.1 +/- 0.2 nmol/500,000 cells). For the air emboli or PMA in vivo experiments, there were no changes in neutrophil activation responses in vitro. Similarly, infusion of control plasma did not result in reduced neutrophil O2- release. These results show that alterations in the inflammatory potential of neutrophils may occur in vivo and that such alterations appear to be dependent on the mechanism and agent by which lung injury is produced.
authors.affiliation: Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: K H
authors.initials: KH
authors.lastname: Albertine
authors.forename: F
authors.initials: F
authors.lastname: Cerasoli
authors.forename: M V
authors.initials: MV
authors.lastname: Tahamont
authors.forename: Y
authors.initials: Y
authors.lastname: Ishihara
authors.forename: J T
authors.initials: JT
authors.lastname: Flynn
authors.forename: S P
authors.initials: SP
authors.lastname: Peters
authors.forename: M H
authors.initials: MH
authors.lastname: Gee
mesh_terms: D000818:Animals; D008168:Lung / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D012756:Sheep; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D013481:Superoxides; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate