title: Plasma activation of neutrophil CD18 after skeletal muscle ischemia: a potential mechanism for late systemic injury.
abstract: Reperfusion of acutely ischemic skeletal muscle is associated with neutrophil activation, which may augment local injury or cause damage to distant organs. Polymorphonuclear neutrophil glycoprotein CD18 plays a role in this injury, since its blockade substantially reduces damage; however, its mechanisms of control during reperfusion are poorly understood. The purpose of this study was to investigate the importance of circulating plasma factors to CD18-dependent neutrophil function during reperfusion and to relate these to quantitative expression of CD18. Eight rabbits were subjected to hindlimb ischemia for 5 h, followed by 48 h of reperfusion. Plasma collected at seven intervals was incubated with unstimulated neutrophils from uninjured rabbits. CD18-specific neutrophil activation was evaluated by quantifying adherence to protein-coated polystyrene and by measuring oxidant production, detected by chemiluminescence after exposure to complement-opsonized zymosan. CD18 was quantified cytofluorometrically. Plasma collected at end ischemia and during early reperfusion affected no significant alterations of adhesion, oxidant production, or CD18. Late reperfusion plasma (between 8 and 48 h) significantly increased adherence and oxidant production (to 4.11 +/- 0.61 and 2.60 +/- 0.32 times the values of preischemic plasma, P < 0.006). Peak adherence, oxidant production, and CD18 expression were evoked synchronously by 24 h plasma. CD18 expression increased only at 24 h and did not increase proportional to increases in adherence and oxidant production. Control plasma (nonischemic, n = 5) elicited no significant differences of any inflammatory measure during sham ischemia or reperfusion. These results indicate that endogenous mediators may evoke a progressive systemic inflammatory response after ischemia by stimulating CD18-dependent neutrophil function in a delayed but prolonged manner.
authors.affiliation: R. Fraser Elliot Vascular Surgery Research Laboratory, Toronto Hospital, University of Toronto, Ontario, Canada.
authors.forename: P F
authors.initials: PF
authors.lastname: Petrasek
authors.forename: T F
authors.initials: TF
authors.lastname: Lindsay
authors.forename: A D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: P M
authors.initials: PM
authors.lastname: Walker
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000276:immunology*; D002448:Cell Adhesion; D005260:Female; D007511:Ischemia / Q000097:blood / Q000276:immunology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010949:Plasma / Q000502:physiology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology
chemical_list: D018821:CD18 Antigens; D017382:Reactive Oxygen Species