Complement activation by the hydroxyl radical during intestinal reperfusion.
This study examines the hypothesis that hydroxyl radical (OH.) generation during intestinal reperfusion activates the complement system forming the potent chemotaxin C5a. Anesthetized Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IIR). Complement (C) activation was assessed by measuring total plasma C activity and C5a-related chemotaxis and leukoaggregation. Dimethylthiourea and the iron chelator deferoxamine were utilized to assess the role of the OH. in the activation of C in this model. Sham-operated animals served as controls. Total plasma C activity of animals sustaining IIR was 64% of controls (p < .05). Plasma of animals sustaining IIR induced greater chemotaxis and leukoaggregation than plasma from sham-operated groups (p < .05). Treatment of IIR plasma with anti-C5a antibody ameliorated the enhanced leukoaggregation characteristic of IIR plasma. Pretreatment with dimethylthiorea and deferoxamine prevented reperfusion-induced activation of complement and inhibited the chemotactic activity of plasma from IIR animals. These data are consistent with the hypothesis that IIR activates complement and that the OH. generated during reperfusion may be one mechanism by which C is activated in this injury model.
Turnage
R H
RH
Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9031, USA.
Magee
J C
JC
Guice
K S
KS
Myers
S I
SI
Oldham
K T
KT
D000818:Animals; D002630:Chemotactic Factors / Q000096:biosynthesis; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D017665:Hydroxyl Radical / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000293:injuries*; D008297:Male; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology* / Q000503:physiopathology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D002630:Chemotactic Factors; D017665:Hydroxyl Radical; D015936:Complement C5a; C038983:1,3-dimethylthiourea; D013890:Thiourea; D003676:Deferoxamine