title: Inhibition of heme oxygenase-1 in microvascular lung pericytes diminishes at high concentrations of an inflammatory mediator.
abstract: Post-traumatic inflammation and sepsis induce changes in the lung microvasculature causing increased permeability. Pericytes, contractile cells positioned abluminally to endothelial cells, play a role in regulating this response. An in vitro model of microvascular lung pericytes (MLP) was used to investigate the effect of inhibiting heme oxygenase-1 (HO-1), a stress-induced enzyme, in the presence of varying levels of lipopolysaccharide (LPS), a mediator in the initiation of inflammation, on pericyte contractility. Rat MLP were cultured on collagen gel matrices. Cells were exposed to three concentrations of LPS in the presence of zinc protoporphyrin IX (ZnPP-9), a known inhibitor of HO-1. After 24 hours, the surface area of the collagen disks was quantified, thereby measuring pericyte contraction. ZnPP-9 caused a significant attenuation of the LPS-induced relaxation of the pericytes (P < or = 0.003). The effects of ZnPP-9, however, depended on the concentration of LPS to which the pericytes were exposed. Greater concentrations of LPS decrease the attenuating power of ZnPP-9. The inhibition of HO-1 diminished MLP relaxation triggered by LPS. The effect of ZnPP-9, however, is dependent on the concentration of LPS to which the MLP are exposed, indicating its saturation. ZnPP-9 may antagonize the microvascular response to trauma.
authors.affiliation: Department of Surgery, Wayne State University, Detroit, Michigan, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Harvey
authors.forename: James G
authors.initials: JG
authors.lastname: Tyburski
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Steffes
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Carlin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D051547:Heme Oxygenase-1; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D020286:Pericytes / Q000187:drug effects*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1