title: Neutrophil depletion attenuates interleukin-8 production in mild-overstretch ventilated normal rabbit lung.
abstract: OBJECTIVE
  Acute lung injury induced by lung overstretch is associated with neutrophil influx, but the pathogenic role of neutrophils in overstretch-induced lung injury remains unclear.
  
  
  METHODS
  To assess the contribution of neutrophils, we compared the effects of noninjurious large tidal volume (Vt) ventilation on lungs in normal and neutrophil-depleted animals.
  
  
  METHODS
  Research animal laboratory.
  
  
  METHODS
  Twenty-six male Japanese white rabbits.
  
  
  METHODS
  Animals were mechanically ventilated for 4 hrs with one of the three following protocols: large Vt (20 mL/kg), small Vt (8 mL/kg), and large Vt (20 mL/kg) with neutrophil depletion achieved by a single dose of vinblastine injection (0.75 mg/kg) intravenously 4 days before the experiment.
  
  
  RESULTS
  Large Vt ventilation produced alveolar neutrophil influx compared with low Vt (p =.002) without evidence of edema or increased epithelial permeability. The neutrophil influx was accompanied by increases in interleukin-8 in bronchoalveolar lavage fluid (p =.04). Immunohistochemistry of large Vt lungs showed increased interleukin-8 staining in bronchial epithelial cells, alveolar epithelium, alveolar macrophages, and smooth muscles of pulmonary vessels. Neutrophil depletion attenuated the interleukin-8 increase in the lung. Large Vt did not increase plasma interleukin-8 or tumor necrosis factor-alpha in plasma and bronchoalveolar lavage fluid. No expression of p-selectin or intercellular adhesion molecule-1 was observed.
  
  
  CONCLUSIONS
  Cyclic overstretching of normal rabbit lungs with noninjurious large Vt produced neutrophil influx and interleukin-8 increase in bronchoalveolar lavage fluid. Production of pulmonary interleukin-8 by lung overstretch might require the interaction between resident lung cells and migrated neutrophils. This study suggests that large Vt ventilation potentiates the predisposed, subclinical lung injury, such as nosocomial pneumonia or aspiration of gastric contents.
authors.affiliation: Department of Anesthesiology, School of Medicine, Keio University, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kotani
authors.forename: Toru
authors.initials: T
authors.lastname: Kotani
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Seitaro
authors.initials: S
authors.lastname: Fujishima
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Koh
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawafuji
authors.forename: Eiji
authors.initials: E
authors.lastname: Ikeda
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Moriyama
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kotake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morisaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ohashi
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Yuh-Chin T
authors.initials: YC
authors.lastname: Huang
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
mesh_terms: D000818:Animals; D016209:Interleukin-8 / Q000096:biosynthesis*; D009504:Neutrophils / Q000502:physiology*; D011661:Pulmonary Stretch Receptors / Q000502:physiology; D011817:Rabbits; D012121:Respiration, Artificial / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000276:immunology
chemical_list: D016209:Interleukin-8