Heme oxygenase modulates selectin expression in different regional vascular beds.
Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin, iron, and CO. The inducible isoform (HO-1) has been implicated as a modulator of the inflammatory response. HO-1 activity can be induced by hemin and inhibited with zinc protoporphyrin IX (ZnPP). Using these reagents, we assessed the possibility that HO-1 modulates the inflammatory response by altering the expression of endothelial cell adhesion molecules. Endotoxin (lipopolysaccharide, LPS)-induced expression of P- and E-selectin expression was quantified in different vascular beds of the rat using the dual radiolabeled monoclonal antibody technique. Pretreatment with hemin attenuated, whereas ZnPP treatment exacerbated, the increased selectin expression normally elicited by LPS. Biliverdin, at an equimolar dosage, was as effective as hemin in attenuating LPS-induced selectin expression in the lung, kidneys, liver, and intestines. These findings indicate that the anti-inflammatory properties of HO-1 may be related to an inhibitory action of P- and E-selectin expression in the vasculature. Biliverdin (or its metabolite, bilirubin), rather than CO, may account for this action of HO-1 on endothelial cell adhesion molecule expression.
Vachharajani
T J
TJ
Division of Nephrology, Department of Molecular and Cellular Physiology and Medicine, Louisiana State University, Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Work
J
J
Issekutz
A C
AC
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001664:Biliverdine / Q000494:pharmacology; D004195:Disease Models, Animal; D019040:E-Selectin / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology*; D007422:Intestines / Q000098:blood supply / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology*; D009928:Organ Specificity; D019007:P-Selectin / Q000096:biosynthesis*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D019007:P-Selectin; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine