Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis1

Visner, Gary; Lu, Fuhua; Zhou, Hailan; Latham, Christopher; Agarwal, Anupam; Zander, Dani S.

doi:10.1097/01.tp.0000080069.61917.18

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…While pharmacologic induction of HO-1 did not alter rejection in this model (67), Song and coworkers recently demonstrated anti-inflammatory and antiapoptotic effects of exogeneous CO administration in a rat orthotopic lung transplantation model (68). More recently, Minamoto and colleagues demonstrated a protective role for HO-1 in a tracheal transplant model of BO (69).…”

Section: Bronchiolitis Obliterans/lung Transplantationmentioning

confidence: 83%

The Role of Heme Oxygenase-1 in Pulmonary Disease

Fredenburgh

Perrella

Mitsialis

2007

Am J Respir Cell Mol Biol

185

165

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Heme oxygenase (HO)-1, the inducible isoform of heme oxygenase, is a cytoprotective enzyme that plays a central role in the defense against oxidative and inflammatory insults in the lung. HO-1 catalyzes the degradation of heme, a potent oxidant, into biliverdin, iron, and carbon monoxide (CO). These downstream products of heme catabolism have recently been found to mediate the antioxidant, antiapoptotic, antiproliferative, vasodilatory, and anti-inflammatory properties of HO-1. Although absence of HO-1 is rare in humans, a number of HO-1 promoter polymorphisms have been identified that may influence HO-1 expression in vivo and lead to disease states. This review will summarize studies that implicate HO-1 and heme metabolites in the pathophysiology of pulmonary disease and discuss recent advances in the therapeutic applications of HO-1.Keywords: HO-1; polymorphism; ARDS; pulmonary hypertension; COPD THE ROLE OF HEME OXYGENASE-1 IN PULMONARY DISEASEHeme oxygenase (HO)-1, the inducible isoform of heme oxygenase, plays a critical role in defending the lung against inflammatory and oxidant-induced cellular and tissue injury. This cytoprotective enzyme catalyzes the degradation of heme, a potent oxidant, to generate biliverdin-IX␣, iron, and carbon monoxide (CO) (Figure 1) (1). Biliverdin-IX␣ is converted to bilirubin-IX␣, a potent endogenous antioxidant (2), with recently recognized anti-inflammatory properties (3), while iron is sequestered by ferritin, leading to additional antioxidant (4) and antiapoptotic (5) effects. CO has numerous biological functions, including anti-inflammatory properties (6, 7), and shares many similarities with nitric oxide (NO), such as its ability to inhibit smooth muscle cell proliferation (8, 9) and platelet aggregation (10), as well as modulate vascular tone by increasing cGMP levels (11).In the lung, HO-1 is expressed in various cells types, including type II pneumocytes and alveolar macrophages, and is induced by heme (12), hypoxia (13,14), hyperoxia (15), and NO (16), as well as endotoxin and proinflammatory cytokines (e.g., IL-6, (Received in final form September 3, 2006 ) This work was funded by T32 HL007633-21 (L.E.F.), RO1 HL60788 (M.A.P.), and R01 HL55454 (S.A.M.) from the National Institutes of Health.

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Section: Bronchiolitis Obliterans/lung Transplantationmentioning

confidence: 83%

The Role of Heme Oxygenase-1 in Pulmonary Disease

Fredenburgh

Perrella

Mitsialis

2007

Am J Respir Cell Mol Biol

185

165

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“…27 Our laboratory and others have shown that the integrity of the epithelium is critical in preventing the development of the OB-like lesion in the mouse tracheal transplant model. 13,28,29 Stabilization of the epithelium may prevent the formation of granulation tissue. There was less epithelial loss in the pirfenidonetreated group, although to a lesser degree than the reduction of intraluminal granulation tissue or fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone Inhibits Obliterative Airway Disease in Mouse Tracheal Allografts

Zhou

Latham

Zander

et al. 2005

The Journal of Heart and Lung Transplantation

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“…At this time, it is difficult to envision how seeding of epithelial cells could be performed in recipients of lung transplants, although the use of recipient stem cells may be promising for development of a similar treatment. A more plausible approach to prevent OB development would be protection of airway epithelial cells by activation of "protective genes," such as HO-1, 34 which may be capable of reducing local inflammation at the epithelial level in cases of allograft reactivity. This could be achieved by exposure of donor lung to carbon monoxide, a treatment shown to be effective in a rat lung transplantation model.…”

Section: Discussionmentioning

confidence: 99%