Polymerized hemoglobin induces heme oxygenase-1 protein expression and inhibits intercellular adhesion molecule-1 protein expression in human lung microvascular endothelial cells.
BACKGROUND
Our clinical trials using a polymerized hemoglobin solution (PolyHb) as a red cell substitute in severely injured patients suggested that this hemoglobin-based oxygen carrier has a systemic antiinflammatory effect. Heme oxygenase-1 (HO-1) has recently been shown to be cytoprotective, and is known to be induced by heme moieties. We investigated the effects of this hemoglobin-based oxygen carrier on HO-1 induction and proinflammatory activation of pulmonary endothelium.


METHODS
Human lung microvascular endothelial cells were grown to confluence and preincubated with either cell media (control) or with an equal volume mixture of polymerized hemoglobin/cell media (experimental). The cell cultures were subsequently stimulated with lipopolysaccharide. HO-1 expression was detected by protein immunoblot and further quantified by ELISA; intercellular adhesion molecule-1 protein expression was measured by flow cytometry.


RESULTS
Polymerized hemoglobin induced synthesis of HO-1 protein in human lung microvascular endothelial cells and, concurrently, inhibited lipopolysaccharide-induced intercellular adhesion molecule-1 protein cell surface expression.


CONCLUSIONS
Polymerized hemoglobin attenuates lipopolysaccharide-stimulated expression of intercellular adhesion molecule-1 protein, which is associated with upregulation of the cytoprotective protein HO-1 in human pulmonary endothelial cells. This antiinflammatory effect offers a novel mechanism by which hemoglobin-based oxygen carrier solutions may be exploited therapeutically as resuscitative fluids.
Cheng
Aaron M
AM
Department of Surgery, University of Colorado Health Sciences Center/Denver Health Medical Center, 80204, USA.
Moore
Ernest E
EE
Johnson
Jeffrey L
JL
Walsh
Mark D
MD
Ao
Lihua
L
Moore
Peter K
PK
Banerjee
Anirban
A
D000704:Analysis of Variance; D001802:Blood Substitutes / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006454:Hemoglobins; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000098:blood supply* / Q000166:cytology*; D008565:Membrane Proteins; D008833:Microcirculation; D015854:Up-Regulation / Q000187:drug effects
D001802:Blood Substitutes; D006454:Hemoglobins; D008565:Membrane Proteins; C079129:hemoglobin polymer; D018799:Intercellular Adhesion Molecule-1; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1