Heme-oxygenase-1 mRNA expression affects hemorrhagic shock-induced leukocyte adherence.
BACKGROUND
Hemorrhagic shock-related leukocyte adherence to endothelial cells is a key step in microvascular injury-related organ damage. Heme-oxygenase-1 (HO-1) metabolizes heme, a potent cytotoxic agent, to carbon monoxide and biliverdin. We hypothesized that changing HO-1 expression would change leukocyte adherence after hemorrhagic shock.


METHODS
Rats were administered hemin, zinc protoporphyrin, or vehicle 6 hours before surgery. HO-1 expression was determined by reverse-transcriptase polymerase chain reaction in various tissues. Shock was induced in urethane-anesthetized animals by decreasing mean arterial blood pressure to 40 mm Hg for 60 minutes, followed by standard resuscitation measures. Leukocyte adherence was measured by intravital microscopy in rat mesenteric venules.


RESULTS
Hemin, hemorrhagic shock, and the combination resulted in significantly increased HO-1 expression, whereas zinc-protoporphyrin (ZNPP) resulted in significantly decreased leukocyte adherence. After hemorrhagic shock and hemin administration, leukocyte adherence was significantly decreased 60 minutes into resuscitation (7.92 +/- 2.29 vs. 4.84 +/- 0.71 cells/100 microm, p < 0.05) and significantly increased after ZNPP plus shock (14.08 +/- 3.95, p <or= 0.01).


CONCLUSIONS
The results demonstrate that hemin increases and ZNPP decreases HO-1 mRNA expression and attenuates hemorrhagic shock-induced leukocyte adherence, whereas ZNPP decreases it. These results suggest that by changing HO-1 expression, leukocyte adherence resulting from oxidant injury may be altered.
Moncure
Michael
M
Department of Surgery, University of kansas School of Medicine, Kansas City, Kansas 66160-7308, USA. mmoncure@kumc.edu
Chen
Lijun
L
Childs
Ed W
EW
Smalley
David
D
Udobi
Kahdi F
KF
Cheung
Laurence Y
LY
D000818:Animals; D002448:Cell Adhesion; D005786:Gene Expression Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000378:metabolism* / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D012333:RNA, Messenger; D016028:Receptors, Leukocyte-Adhesion; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1