Inactivation of synovial fluid α<sub>1</sub>‐antitrypsin by exercise of the inflamed rheumatoid joint

Zhang, Zhi; Farrell, A J; Blake, David R.; Chidwick, Keith; Winyard, Paul G.

doi:10.1016/0014-5793(93)80123-c

Cited by 28 publications

(12 citation statements)

References 22 publications

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“…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 synovial fluids. 20,21 AT contains methionine at the "P1 position," which is located in the reactive site, and determines the specificity of inhibition.…”

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confidence: 99%

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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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confidence: 99%

“…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 synovial fluids. 20,21 AT contains methionine at the "P1 position," which is located in the reactive site, and determines the specificity of inhibition.…”

mentioning

confidence: 99%

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

Mashiba

Wada

Takeya

et al. 2001

ATVB

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“…Consequently, there is significant inactivation of the elastase inhibitory activity within rheumatoid synovial fluid [2 11. Following rest/ exercise cycles in patients with inflammatory synovitis the proportion of functionally active API falls [22]. This exercise-mediated inactivation does not appear to be due to proteolysis, since SDSIPAGE with Western blotting reveals no change in the proportions of intact and cleaved API.…”

Section: Volume 21mentioning

confidence: 90%

Oxidative stress and its control: A pathogenetic role in inflammatory joint disease

Fairburn

Stevens

Winyard

et al. 1993

Biochemical Society Transactions

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“…Methionine can be attacked by various oxidants, such as peroxide, hydroxyl radicals, hypochloride, chloramines and peroxynitrite (Vogt, 1995;Rahman and MacNee, 1996), which are mainly produced by activated inflammatory cells. Oxidized AT (Ox-AT) in vivo has been confirmed by the finding that the inactive AT purified from the inflammatory synovial fluid contains methionine sulphoxide residues, and that 41% of total AT in the fluid is inactive, oxidized and/or cleaved (Zhang et al, 1993). Smoking is a major external source of oxidants (Rahman and MacNee, 1996;Church and Pryor, 1985;Schaberg et al, 1992).…”

Section: Oxidized Atmentioning

confidence: 98%

The Role of Alpha-1 Antitrypsin in Emphysema

Alam¹,

Mahadeva²

2012

Emphysema

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Inactivation of synovial fluid α₁‐antitrypsin by exercise of the inflamed rheumatoid joint

Cited by 28 publications

References 22 publications

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

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

Oxidative stress and its control: A pathogenetic role in inflammatory joint disease

The Role of Alpha-1 Antitrypsin in Emphysema

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Inactivation of synovial fluid α1‐antitrypsin by exercise of the inflamed rheumatoid joint

Cited by 28 publications

References 22 publications

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

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

Oxidative stress and its control: A pathogenetic role in inflammatory joint disease

The Role of Alpha-1 Antitrypsin in Emphysema

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Product

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Inactivation of synovial fluid α₁‐antitrypsin by exercise of the inflamed rheumatoid joint

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

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