Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system.
The respiratory system, including the lung and upper airways, succumbs to injury and disease through acute or chronic exposures to adverse environmental agents, in particular, those that promote increased oxidative or inflammatory processes. Cigarette smoke and other forms of particulate or gaseous air pollution, allergens, microorganisms infections, and changes in inspired oxygen may contribute to lung injury. Among the intrinsic defenses of the lung, the stress protein heme oxygenase-1 constitutes an inducible defense mechanism that can protect the lung and its constituent cells against such insults. Heme oxygenases degrade heme to biliverdin-IXalpha, carbon monoxide, and iron, each with candidate roles in cytoprotection. At low concentrations, carbon monoxide can confer similar cyto and tissue-protective effects as endogenous heme oxygenase-1 expression, involving antioxidative, antiinflammatory, antiproliferative, and antiapoptotic effects. Lung protection by heme oxygenase-1 or its enzymatic reaction products has been demonstrated in vitro and in vivo in a number of pulmonary disease models, including acute lung injury, cigarette smoke-induced lung injury/chronic obstructive pulmonary disease, interstitial lung diseases, ischemia/reperfusion injury, and asthma/airway inflammation. This review summarizes recent findings on the functions of heme oxygenase-1 in the respiratory system, with an emphasis on possible roles in disease progression and therapies.
Ryter
Stefan W
SW
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. Ryters@upmc.edu
Kim
Hong Pyo
HP
Nakahira
Kiichi
K
Zuckerbraun
Brian S
BS
Morse
Danielle
D
Choi
Augustine M K
AM
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D020011:Protective Agents / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism*
D020011:Protective Agents; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1