title: Irradiation causes biphasic neutrophilic granulocyte phagocytic function.
abstract: OBJECTIVE
  The anti-inflammatory effect of low-dose radiotherapy is clinically well described. Nevertheless, until now neither the optimal dose nor the background of tissue reactions have been defined. The current study examines the influence of low radiation doses on neutrophilic granulocyte function, which could be helpful in finding the optimal dose for either stimulation or suppression of anti-inflammatory activity.
  
  
  METHODS
  Lymphoprep density gradient-purified neutrophilic granulocytes of three voluntary, healthy donors were used for all experiments. Granulocytes were incubated 48 h in RPMI 1640 and irradiated with single doses of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, and 12 Gy using a (137)Cs IBL 437L irradiator. Their function was assessed by measuring granulocytic release of reactive oxygen species (ROS) with luminol-enhanced chemiluminescence after stimulation with phorbol myristate acetate (PMA).
  
  
  RESULTS
  Relative changes of ROS release (ROS release before stimulation was set to 100%) increased after stimulation with PMA (mean +/- standard deviation [SD]): 0 Gy: 147.6% +/- 60%; 0.5 Gy: 153.6% +/- 70%; 1.0 Gy: 164.9% +/- 63%; 1.5 Gy: 177.8% +/- 66%; 2.0 Gy: 162.5% +/- 57%; 2.5 Gy: 156.2% +/- 60%; 3.0 Gy: 159.2% +/- 60%; 3.5 Gy: 126.9% +/- 55%; 4.0 Gy: 137.9% +/- 71%; 6.0 Gy: 148.3% +/- 65%; 12.0 Gy: 156.1% +/- 52%. The relative ROS release showed a significant increase at 1.5 Gy (p < 0.001) after PMA stimulation and a significant decrease of ROS release at 3.5 Gy (p < 0.005) and less markedly at 4.0 Gy (p < 0.05). 6.0 and 12.0 Gy showed a significant (p < 0.05) increase again.
  
  
  CONCLUSIONS
  This ex vivo in vitro study on native human neutrophilic granulocytes shows an increase at 1.5 Gy and a significant decrease of granulocyte function at 3.5 and 4.0 Gy, as it was described for different other phenomena in low-dose radiotherapy. These results may provide a further explanation for the local anti-inflammatory effect of low-dose ionizing irradiation.
authors.affiliation: Department of Radiotherapy, Münster University Hospital, Münster, Germany. omicke@uni-muenster.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Micke
authors.forename: Alfred
authors.initials: A
authors.lastname: Haidenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Auer
authors.forename: Sabine
authors.initials: S
authors.lastname: Egger
authors.forename: M Heinrich
authors.initials: MH
authors.lastname: Seegenschmiedt
authors.forename: Paul
authors.initials: P
authors.lastname: Hengster
authors.forename: Alexander F
authors.initials: AF
authors.lastname: DeVries
mesh_terms: D004307:Dose-Response Relationship, Radiation; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D049449:Luminescence; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D010587:Phagocytosis / Q000187:drug effects / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D013755:Tetradecanoylphorbol Acetate