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Citations to this article

Potential Mediator of Inflammation: PHAGOCYTE-DERIVED OXIDANTS SUPPRESS THE ELASTASE-INHIBITORY CAPACITY OF ALPHA1-PROTEINASE INHIBITOR IN VITRO
Harvey Carp, Aaron Janoff
Harvey Carp, Aaron Janoff
Published November 1, 1980
Citation Information: J Clin Invest. 1980;66(5):987-995. https://doi.org/10.1172/JCI109968.
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Potential Mediator of Inflammation: PHAGOCYTE-DERIVED OXIDANTS SUPPRESS THE ELASTASE-INHIBITORY CAPACITY OF ALPHA1-PROTEINASE INHIBITOR IN VITRO

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Abstract

Human polymorphonuclear leukocytes, monocytes, or pulmonary alveolar macrophages, stimulated in vitro by phorbol myristate acetate (PMA), released reactive oxygen species able to suppress the elastase inhibitory capacity (EIC) of human serum. Immunoelectrophoresis using antibodies against α1-proteinase inhibitor (α1-Pi) and elastase showed that inactivation of α1-Pi was responsible for the decreased serum EIC. Treatment of phagocyte-inactivated serum with a reducing agent (dithiothreitol) resulted in significant recovery of EIC, suggesting that α1-Pi had been oxidatively inactivated. Serum EIC was partially protected by superoxide dismutase or catalase. Hydrogen peroxide alone had no effect on serum EIC. Thus, neither H2O2 nor O2− alone, but a product of the two, may have oxidatively inactivated α1-Pi. In support of the foregoing, neutrophils or monocytes from a patient with chronic granulomatous disease failed to produce detectable levels of O2− after incubation with PMA. These cells also failed to suppress serum EIC. In the case of PMA-stimulated polymorphonuclear leukocytes or monocytes, extracellular myeloperoxidase may have also played a role in α1-Pi inactivation since serum EIC was partly protected by azide, cyanide, or the depletion of extracellular chloride. Indeed, in a cell-free system consisting of purified myeloperoxidase, a glucose oxidase-H2O2-generating system, and Cl−, the EIC of human serum or purified α1-Pi could also be suppressed. Omission of any single reactant prevented this effect, as did NaN3 or catalase, suggesting that enzymatically active myeloperoxidase and H2O2 were necessary. Immunoelectrophoresis of myeloperoxidase-inactivated serum showed that, as before, inactivation of α1-Pi was responsible for the decreased EIC. Treating myeloperoxidase-inactivated serum with dithiothreitol led to significant recovery of EIC, again suggesting that oxidative inactivation of α1-Pi had occurred. Oxidative inactivation of α1-Pi in the microenvironment of inflammatory cells, at sites of acute or chronic inflammation, may allow proteases released from these cells to damage adjacent connective tissue components more readily.

Authors

Harvey Carp, Aaron Janoff

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Total citations by year

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Citations to this article in year 1987 (17)

Title and authors Publication Year
Degradation of human glomerular basement membrane by stimulated neutrophils. Activation of a metalloproteinase(s) by reactive oxygen metabolites
SV Shah, WH Baricos, A Basci
Journal of Clinical Investigation 1987
Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase
RC Hubbard, F Ogushi, GA Fells, AM Cantin, S Jallat, M Courtney, RG Crystal
Journal of Clinical Investigation 1987
Ascorbate and cysteine-mediated selective neutralisation of extracellular oxidants during N-formyl peptide activation of human phagocytes
R Anderson, PT Lukey, AJ Theron, U Dippenaar
Agents and Actions 1987
Degradation in vivo of articular cartilage in rheumatoid arthritis and juvenile chronic arthritis by cathepsin G and elastase from polymorphonuclear leukocytes
M Velvart, K Fehr
Rheumatology International 1987
In vivo studies of rat alveolar macrophase microviscosity: Influence of pulmonary surfactant synthesis stimulation
M Luisetti, M Salmona, E Pozzi, M Genghini, L Spialtini, P Masturzo
Lung 1987
Aspects of the Structure, Function, and Applications of Superoxide Dismutas
JV Bannister, WH Bannister, G Rotilio
Critical Reviews in Biochemistry and Molecular Biology 1987
A Biological Role for Ascorbate in the Selective Neutralization of Extracellular Phagocyte-derived Oxidants
R Anderson, PT Lukey
Annals of the New York Academy of Sciences 1987
Elastase-mediated fibrinogenolysis by chemoattractant-stimulated neutrophils occurs in the presence of physiologic concentrations of antiproteinases
JI Weitz, AJ Huang, SL Landman, SC Nicholson, SC Silverstein
Journal of Experimental Medicine 1987
The antioxidant action of human extracellular fluids. Effect of human serum and its protein components on the inactivation of alpha 1-antiproteinase by hypochlorous acid and by hydrogen peroxide
M Wasil, B Halliwell, DC Hutchison, H Baum
Biochemical Journal 1987
Action of hypochlorous acid on the antioxidant protective enzymes superoxide dismutase, catalase and glutathione peroxidase
OI Aruoma, B Halliwell
Biochemical Journal 1987
SC-39026, a specific human neutrophil elastase inhibitor
A Nakao, RA Partis, GP Jung, RA Mueller
Biochemical and Biophysical Research Communications 1987
Hormonal regulation of serum alpha1-antitrypsin and hepatic alpha1-antitrypsin mRNA in rats
SJ Schwarzenberg, HL Sharp, SA Berry, RD Manthei, S Seelig
Biochemical and Biophysical Research Communications 1987
Uptake of Ascorbic Acid by Leukocytes
U Moser
Annals of the New York Academy of Sciences 1987
Acute Effect of Nitrogen Dioxide Exposure on the Functional Activity of Alpha-1-Protease Inhibitor in Bronchoalveolar Lavage Fluid of Normal Subjects
V Mohsenin, JB Gee
American journal of respiratory and critical care medicine 1987
Dog tracheal epithelial cells in culture synthesize sulfated macromolecular glycoconjugates and release them from the cell surface upon exposure to extracellular proteinases
S Varsano, C B Basbaum, L S Forsberg, D B Borson, G Caughey, J A Nadel
Experimental Lung Research 1987
Current Perspectives on Septic Shock
JJ Zimmerman, KA Dietrich
Pediatric Clinics of North America 1987
Effect of Smoking on Functional Activity of Plasma α1-Protease Inhibitor
T Fera, RT Abboud, SS Johal, AM Richter, N Gibson
Chest 1987

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