Oxidative Inactivation of <i>α</i><sub>1</sub>-Proteinase Inhibitor by Alveolar Macrophages from Healthy Smokers Requires the Presence of Myeloperoxidase

Wallaert, B.; Gressier, Bernard; Aerts, C; Mizon, Charlotte; Voisin, C; Mizon, J

doi:10.1165/ajrcmb/5.5.437

Cited by 24 publications

(12 citation statements)

References 28 publications

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“…These findings suggest that the synthesis of peroxynitrite is the major mechanism by which AMs may inactivate antiproteases. In contrast, WALLAERT et al [34] demonstrated that PMA-stimulated AMs do not inactivate α 1 -PI unless myeloperoxidase, released from PMNs, is present. In the cell-free PMN supernatant, we found myeloperoxidase activity and reactive oxygen metabolites, as indicated by the generation of methionine sulphoxide.…”

Section: Discussionmentioning

confidence: 89%

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Vogelmeier¹,

Biedermann²,

Maier³

et al. 1997

Eur Respir J

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Secretory leukoprotease inhibitor (SLPI) and α 1 -protease inhibitor (α 1 -PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and α 1 -PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites.We incubated rSLPI and α 1 -PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs).Under all conditions evaluated, both antiproteases were partially inactivated. The resulting anti-NE activity of rSLPI was not significantly different from that of α 1 -PI after exposure to NCS (p>0.5), chloramines (p>0.6), activated PMNs (p> 0.07) and activated AMs (p>0.9).In conclusion, recombinant secretory leukoprotease inhibitor and α 1 -protease inhibitor lose antineutrophil elastase activity to a similar extent when exposed to conditions that may be present in inflammatory lung disorders.

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Section: Discussionmentioning

confidence: 89%

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Vogelmeier¹,

Biedermann²,

Maier³

et al. 1997

Eur Respir J

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“…A more promising avenue of investigation may be the measurement of circulating or excreted elastin degradation products [15]. Neutrophils may suppress the antiprotease capacity of the ELF through two pathways: the secretion of large quantities of serine proteases that bind antiprotease molecules, and the generation of oxygen-derived free radicals that may inactivate antiproteases either directly [3] or in combination with myeloperoxidase [20]. In the present study, the BAL antielastase activity was lower in samples with higher neutrophil counts, but this tendency did not translate into a statistically significant correlation overall.…”

Section: Discussionmentioning

confidence: 99%

Relationship between bronchoalveolar lavage neutrophil numbers and lavage fluid elastase and antielastase activities

Dent

Rabe

Magnussen

1995

Lung

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Elastase and antielastase activities were measured in bronchoalveolar lavage fluid (BALF) and their relationship to bronchoalveolar lavage (BAL) neutrophil numbers was assessed in order to determine whether the elevated BAL neutrophil count can predict a shift in the elastase/antielastase balance. BAL samples were obtained from 133 randomly selected patients undergoing diagnostic bronchoscopy with BAL. Elastase and antielastase activities were determined using the synthetic substrate MeO-Suc-Ala-Ala-Pro-Val-pNA. In a random subset of 24 samples, the antioxidant capacity was measured as the inhibition of peroxyl radical-mediated oxidation of B-phycoerythrin. Only 7 of the BAL samples exhibited measurable elastase activity and all but one of these had a BAL neutrophil count greater than 100 x 10(3)/ml. Antielastase activity was measurable in 124 samples exhibiting no free elastase activity. There was a tendency for lower antielastase activity to be associated with higher neutrophil numbers, but this did not translate into a statistically significant correlation over all samples. There was no significant correlation between antioxidant capacity and either the neutrophil number or antielastase activity. It is concluded that BAL neutrophil numbers do not, in general, predict the status of elastase/antielastase balance in the epithelial lining fluid and that the antioxidant mechanisms in the epithelial lining fluid do not appear to be related to the antielastase capacity.

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“…20,21 AT contains methionine at the "P1 position," which is located in the reactive site, and determines the specificity of inhibition. Various oxidant radicals such as peroxide, the hydroxyl radical, hypochloride, chloramine, and peroxynitrite 22,23 change the methionine into methionine sulfoxide, and such modified forms of AT lose the inhibitory activity against proteinases. Furthermore, such an oxidized form of AT has the function of monocyte activation.…”

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confidence: 99%

In Vivo Complex Formation of Oxidized α ₁ -Antitrypsin and LDL

Mashiba

Wada

Takeya

et al. 2001

ATVB

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Abstract-An inactivated form of ␣ 1 -antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T-oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehyde-or 4-hydroxy-2-nonenal-modified AT, but neither normal active AT nor trypsin/AT complex. Comigration of apoB and oxidized AT was demonstrated by Western blotting analysis of AT-LDL by means of anti-apoB monoclonal antibody and OxAT-4. A complex of oxidized AT and LDL (AT-LDL) was isolated from human plasma LDL by affinity column with an OxAT-4 antibody-coated carrier. AT-LDL was degraded 4 times more effectively by mouse peritoneal macrophages, but this was not mediated by scavenger receptor class A type I. Localization of AT-LDL was detected in human atherosclerotic lesions of the coronary artery, but distribution of it was not completely identical to that of macrophages. In situ hybridization revealed AT expression by macrophages, which were present in intimal layers of the coronary artery. From these findings, we concluded that AT is produced and oxidized by macrophages, then attached to LDL in the intimal layer of the arterial wall. Although AT-LDL that escapes into the blood stream can be cleared by hepatocytes, the remaining AT-LDL may be taken up by macrophages and contribute to the lipid accumulation in arterial wall cells as the early stage of atherogenesis. Key Words:erine proteinase activity is regulated by a group of inhibitors of the serine proteinases (also called serpin). ␣ 1 -Antitrypsin (AT) is one of the serpin family proteins. It is produced mainly in the liver, and partly by macrophages stimulated by interleukin-6 or lipopolysaccharide. 1-5 At inflammatory sites, AT protects the tissue against damage caused by proteinases derived from white blood cells; in the lung, AT is produced by monocytes, which are stimulated by endotoxin, interleukin-1, and tumor necrosis factor-␣ and protect the alveolar microstructure against excess activity of proteinases. 6,7 After formation of complexes of AT with serine proteinase, AT is cleaved at the site of the serpin reactive loop and changed into the inactive form. 8,9 The resulting 4-kDa carboxy-terminal fragment of 36 residues (C-36) still binds the complex noncovalently, but under denaturing conditions in vitro, the C-36 fragment dissociates from the complex. 10,11 Recent studies have elucidated the biological activities of the C-36 fragment: upregulation of expression of the LDL receptor in HepG2 cells [12][13][14] and induction of cytokine production and CD36 expression in monocytes. 15 Furthermore, it is involved in neutrophil recruitment. 16,17 Thus, not only AT itself but also the byproducts of its enzymatic inhibition possess biological activities at the locus of inflammation.Oxidized AT is another modified form of ␣ 1 -AT, which is found in inflammatory exudates at levels of Ϸ5% to 10% of total AT 18,19 and inflammatory sy...

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Oxidative Inactivation of α₁-Proteinase Inhibitor by Alveolar Macrophages from Healthy Smokers Requires the Presence of Myeloperoxidase

Cited by 24 publications

References 28 publications

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Relationship between bronchoalveolar lavage neutrophil numbers and lavage fluid elastase and antielastase activities

In Vivo Complex Formation of Oxidized α ₁ -Antitrypsin and LDL

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Oxidative Inactivation of α1-Proteinase Inhibitor by Alveolar Macrophages from Healthy Smokers Requires the Presence of Myeloperoxidase

Cited by 24 publications

References 28 publications

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Comparative loss of activity of recombinant secretory leukoprotease inhibitor and alpha 1-protease inhibitor caused by different forms of oxidative stress

Relationship between bronchoalveolar lavage neutrophil numbers and lavage fluid elastase and antielastase activities

In Vivo Complex Formation of Oxidized α 1 -Antitrypsin and LDL

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Oxidative Inactivation of α₁-Proteinase Inhibitor by Alveolar Macrophages from Healthy Smokers Requires the Presence of Myeloperoxidase

In Vivo Complex Formation of Oxidized α ₁ -Antitrypsin and LDL