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.
Harvey Carp, Aaron Janoff
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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 |