title: Systemic neutrophil intrinsic 5-lipoxygenase activity and CD18 receptor expression linked to reperfusion injury.
abstract: OBJECTIVE
  To determine if systemic neutrophil intrinsic 5-lipoxygenase (5-LO) inhibition correlates with decreased expression of surface adhesion molecules and attenuation of ischemia-reperfusion (i/r) injury in guinea pig island skin flaps.
  
  
  METHODS
  Eighty-one adult female Hartley guinea pigs were divided into one control group, three 2-hour ischemia groups, and four 10-hour ischemia groups. Island dorsal skin flaps were developed (except in the control group), and 2 hours before reperfusion, zileutin (a 5-LO inhibitor) or vehicle was administered orally. Postreperfusion systemic neutrophil receptor expression, neutrophil flap infiltration, and flap survival were measured. Neutrophils from whole blood were analyzed for CD18 containing surface receptor expression using monoclonal antibodies and cell associated fluorescence. Neutrophil infiltration into a distal centimeter squared of flap tissue was assessed using myeloperoxidase antibodies, and flap survival was determined within 7 days postoperatively.
  
  
  RESULTS
  Flaps in the treated 2- and 10-hour ischemic groups survived totally intact, while the untreated 10-hour ischemic flaps underwent total necrosis. A significant main effect of the drug was detected using analysis of variance (ANOVA) (P =.0001). Surface receptor detection and neutrophil infiltration were significantly increased in the untreated animals.
  
  
  CONCLUSIONS
  Zileuton, a 5-LO inhibitor, reduces adhesion receptor expression on systemic neutrophils and attenuates i/r injury. Systemic neutrophil intrinsic 5-LO activity and CD18 receptor expression are linked to reperfusion injury and may be fundamental events in its pathogenesis.
authors.affiliation: Department of Otolaryngology, Boston University School of Medicine, Massachusetts, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dolan
authors.forename: K
authors.initials: K
authors.lastname: Hartshorn
authors.forename: C
authors.initials: C
authors.lastname: Andry
authors.forename: D
authors.initials: D
authors.lastname: McAvoy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D018821:CD18 Antigens / Q000276:immunology*; D062109:Dermatologic Surgical Procedures; D005260:Female; D006085:Graft Survival; D006168:Guinea Pigs; D009336:Necrosis; D018375:Neutrophil Activation / Q000276:immunology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D015427:Reperfusion Injury / Q000201:enzymology* / Q000276:immunology* / Q000601:surgery; D012867:Skin / Q000098:blood supply*; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D001094:Arachidonate 5-Lipoxygenase