title: Intravascular neutrophil activation due to carbon monoxide poisoning.
abstract: BACKGROUND
  We hypothesized that platelet-neutrophil interactions occur as a result of acute carbon monoxide (CO) poisoning, and subsequent neutrophil activation triggers events that cause neurologic sequelae.
  
  
  OBJECTIVE
  To identify platelet-neutrophil interactions and neutrophil activation in patients and in animal models, and to establish the association between these intravascular events and changes linked to CO-mediated neurologic sequelae in an animal model.
  
  
  RESULTS
  Blood was obtained from 50 consecutive patients. Abnormalities were variable depending on the carboxyhemoglobin level at study admission and duration of CO exposure. Platelet-neutrophil aggregates were detected and plasma myeloperoxidase (MPO) concentration was significantly elevated in those with confirmed CO poisoning. Among patients exposed to CO for over 3 h, flow cytometry scans of neutrophils revealed increased surface expression of CD18 and, in some groups, MPO on the cell surface. Animal models revealed consistent evidence of platelet-neutrophil aggregates, neutrophil activation and surface MPO, and plasma MPO elevation. MPO was deposited along the brain vascular lining and colocalized with nitrotyrosine. CO poisoning caused abnormalities in the charge pattern of myelin basic protein (MBP), changes linked to adaptive immunologic responses responsible for neurologic sequelae in this model. Changes did not occur in thrombocytopenic rats, those receiving tirofiban to inhibit platelet-neutrophil interactions, or those receiving L-nitroarginine methyl ester to inhibit nitric oxide synthesis. Alterations in MBP did not occur in CO-poisoned knockout mice lacking MPO.
  
  
  CONCLUSIONS
  Acute CO poisoning causes intravascular neutrophil activation due to interactions with platelets. MPO liberated by neutrophils mediates perivascular oxidative stress, which is linked to immune-mediated neurologic sequelae.
authors.affiliation: Institute for Environmental Medicine, Department of Emergency Medicine, University of Pennsylvania, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6068, USA. sthom@mail.med.upenn.edu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Han
authors.forename: James M
authors.initials: JM
authors.lastname: Clark
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Hardy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D002249:Carbon Monoxide Poisoning / Q000150:complications* / Q000503:physiopathology*; D015550:Cell Degranulation; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D018375:Neutrophil Activation / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats
chemical_list: D009195:Peroxidase