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1 Division of Nephrology, Department of
Molecular and Cellular Physiology and Medicine, Louisiana State
University, Health Sciences Center, Shreveport, Louisiana
71130-3932; and 2 Department of Pediatrics,
Dalhousie University, Halifax, Nova Scotia, Canada B3J
3G9
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.
E-selectin; P-selectin; inflammation; biliverdin; endotoxin