title: A new approach to the investigation of oxidative injury to the pulmonary endothelium: use of angiotensin-converting enzyme as a marker.
abstract: Oxidative injury to the pulmonary endothelium plays and important role in lung pathology. Oxidants (that accumulate in lung tissue upon hyperoxia or hypoxia, or are released from activated leukocytes) can destroy endothelial cells. Investigation of the mechanisms of oxidative endothelial injury and the choice of valid criteria with which to measure these pathological deviations are therefore of great importance. Among the criteria used to assess endothelial injury (e.g. accumulation of the products of lipid peroxidation, enhancement of pulmonary microvascular permeability, morphological changes), monitoring of angiotensin-converting enzyme (ACE) is of great interest because it is associated with the endothelial surface and thus reflects endothelial status. Assessment of lung rather than serum ACE activity is the best indicator of endothelial injury. For a comprehensive evaluation of endothelial status, not only total ACE activity in lung tissue but also ACE accessibility to circulating ligands should be monitored. Radiolabelled ACE substrates have been used as ligands in the perfusion of isolated lungs of experimental animals. Radiolabelled monoclonal antibody (Mab) to ACE has been proposed as an alternative ligand, because a drastic decrease in uptake of this Mab by the lungs upon lung injury has been shown. This approach is extremely sensitive: a decrease in antibody uptake occurs even upon mild (nonoedematous) oxidative lung injury, when other indicators, such as lung and serum ACE activity, accumulation of the products of lipid peroxidation, and microvascular permeability, remain unchanged. The use of radiolabelled Mab allows the pulmonary microvascular status to be monitored by gamma-scintigraphy.
authors.affiliation: Institute of Experimental Cardiology, Academy of Medical Sciences of the USSR, Moscow.
authors.forename: V R
authors.initials: VR
authors.lastname: Muzykantov
authors.forename: S M
authors.initials: SM
authors.lastname: Danilov
mesh_terms: D015415:Biomarkers; D004727:Endothelium / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000378:metabolism*; D010100:Oxygen / Q000009:adverse effects*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D007703:Peptidyl-Dipeptidase A; D013890:Thiourea; D010100:Oxygen; C005277:alpha-naphthyl thiourea