En. Atochina et al., NORMOXIC LUNG ISCHEMIA REPERFUSION ACCELERATES SHEDDING OF ANGIOTENSIN-CONVERTING ENZYME FROM THE PULMONARY ENDOTHELIUM/, American journal of respiratory and critical care medicine, 156(4), 1997, pp. 1114-1119
Citations number
33
Categorie Soggetti
Emergency Medicine & Critical Care","Respiratory System
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 inju
ry produced. I/R led to a time-dependent increase in ACE activity in t
he 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 lungs was as
sociated with an aqueous phase of extracted perfusates, thus indicatin
g that I/R accelerates shedding of the hydrophilic form of ACE from th
e plasma membrane. To specifically assess ACE localized on the luminal
surface of the pulmonary endothelium, we perfused rat lungs with a ra
diolabeled monoclonal antibody (mAb) to ACE (anti-ACE mAb 9B9). Pulmon
ary 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 u
ptake of nonspecific [I-125]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 incre
ase in [I-125]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 vascula endothelium
.