title: Divergent roles of glutathione peroxidase-1 (Gpx1) in regulation of leukocyte-endothelial cell interactions in the inflamed cerebral microvasculature.
abstract: OBJECTIVE
  The aim of this study was to assess the ability of Gpx1 to regulate leukocyte-endothelial cell interactions in the cerebral microcirculation under inflammatory conditions associated with oxidative stress.
  
  
  METHODS
  To induce cerebral inflammation, wild-type and Gpx1(-/-) mice underwent systemic treatment with TNF or transient focal cerebral ischemia via MCAO. Leukocyte rolling and adhesion in cerebral postcapillary venules were assessed by intravital microscopy.
  
  
  RESULTS
  Absence of Gpx1(-/-) resulted in increased cerebral oxidant production in response to TNF. Under these conditions, leukocyte rolling in cerebral venules was significantly elevated in Gpx1(-/-) mice, whereas leukocyte adhesion was lower than that in wild-type mice. Despite this, expression of key adhesion molecules did not differ between the strains. Following MCAO, Gpx1(-/-) mice displayed significant reductions in rolling and adhesion associated with severe blood flow restriction. In contrast, following treatment with the anti-oxidant ebselen to equalize postischemic cerebral blood flow in wild-type and Gpx1(-/-) mice, absence of Gpx1 was associated with significant elevations in leukocyte interactions.
  
  
  CONCLUSIONS
  These data show that under some inflammatory conditions, Gpx1 regulates leukocyte-endothelial cell interactions in the cerebral microvasculature, but that this is affected by the nature of the inflammatory insult.
authors.affiliation: Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.
authors.forename: Connie H Y
authors.initials: CH
authors.lastname: Wong
authors.forename: Latasha D
authors.initials: LD
authors.lastname: Abeynaike
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hickey
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D002450:Cell Communication; D002560:Cerebrovascular Circulation; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation; D020293:Vasculitis, Central Nervous System / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse