Normoxic lung ischemia/reperfussion Accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium

Elena Nikolaevna Atochina, V. R. Muzykantov, A. B. Al-Mehdi, S. M. Danilov, A. B. Fisher

    Research output: Contribution to journalArticle

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    Abstract

    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 989 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 in- crease 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.

    Original languageEnglish
    Pages (from-to)1114-1119
    Number of pages6
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume156
    Issue number4 I
    Publication statusPublished - 1997

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    Peptidyl-Dipeptidase A
    Endothelium
    Ischemia
    Reperfusion
    Lung
    Monoclonal Antibodies
    Pulmonary Edema
    Immunoglobulin G
    Weights and Measures
    Vascular Endothelium
    Capillary Permeability
    Lung Injury
    Reperfusion Injury
    Body Weight
    Cell Membrane

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine

    Cite this

    Normoxic lung ischemia/reperfussion Accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium. / Atochina, Elena Nikolaevna; Muzykantov, V. R.; Al-Mehdi, A. B.; Danilov, S. M.; Fisher, A. B.

    In: American Journal of Respiratory and Critical Care Medicine, Vol. 156, No. 4 I, 1997, p. 1114-1119.

    Research output: Contribution to journalArticle

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