Normoxic lung ischemia/reperfusion accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium.
Normoxic lung ischemia/reperfusion (I/R) leads to oxidative injury of the pulmonary tissue. We analyzed angiotensin-converting enzyme (ACE) in perfused rat lungs upon I/R in order to assess the endothelial injury produced. I/R led to a time-dependent increase in ACE activity in the perfusate, from 145+/-14 mU to 252+/-1 mU, and to reduction of ACE activity in the lung tissue homogenate, from 29.7+/-2.3 U to 22.7+/-1.7 U. About 80% of ACE activity in control and I/R rat lungs was associated with an aqueous phase of extracted perfusates, thus indicating that I/R accelerates shedding of the hydrophilic form of ACE from the plasma membrane. To specifically assess ACE localized on the luminal surface of the pulmonary endothelium, we perfused rat lungs with a radiolabeled monoclonal antibody (mAb) to ACE (anti-ACE mAb 9B9). Pulmonary uptake of mAb 9B9 with I/R was reduced from 32.1+/-1.7% to 24.8+/-0.9%. In contrast, I/R led to a marked increase in the pulmonary uptake of nonspecific [125I]IgG, from 0.17+/-0.02% to 0.67+/-0.04%. Lung wet weight was equal to 0.78+/-0.08% of body weight in the I/R group versus 0.57+/-0.02% at the control level. The observed increase in [125I]IgG uptake and wet lung weight indicate that I/R causes an increase in lung vascular permeability. These results indicate that normoxic lung I/R induces injury to the pulmonary vascular endothelium.
Atochina
E N
EN
Institute for Environmental Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Muzykantov
V R
VR
Al-Mehdi
A B
AB
Danilov
S M
SM
Fisher
A B
AB
D000818:Animals; D000911:Antibodies, Monoclonal; D002199:Capillary Permeability; D002462:Cell Membrane / Q000201:enzymology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000166:cytology; D008297:Male; D051379:Mice; D010100:Oxygen / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011651:Pulmonary Artery / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology*; D012121:Respiration, Artificial
D000911:Antibodies, Monoclonal; D007703:Peptidyl-Dipeptidase A; D010100:Oxygen