The interaction of α1-antitrypsin with trypsin, chymotrypsin and human leukocyte elastase as revealed by end group analysis

Martodam, Raymond R.; Liener, Irvin E.

doi:10.1016/0005-2795(81)90199-9

Cited by 16 publications

(6 citation statements)

References 39 publications

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“…The binding of α 1 PI to the catalytic site within HLE interrupts the electron transfer mechanism of the catalytic triad. Cleavage is not completed, and α 1 PI is not cleaved [25]. Interaction of α 1 PI with serine proteinases other than HLE, for example furin, can produce cleavage, and in this case, α 1 PI is acting as a substrate, not an inhibitor [26].…”

Section: Introductionmentioning

confidence: 99%

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

et al. 2012

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BackgroundThe regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLECS), it acts not as a proteinase, but as a receptor for α1proteinase inhibitor (α1PI, α1antitrypsin, SerpinA1). Binding of α1PI to HLECS forms a motogenic complex. We previously demonstrated that α1PI deficiency attends HIV-1 disease and that α1PI augmentation produces increased numbers of immunocompetent circulating CD4+ lymphocytes. Herein we investigated the mechanism underlying the α1PI deficiency that attends HIV-1 infection.Methods and FindingsActive α1PI in HIV-1 subjects (median 17 µM, n = 35) was significantly below normal (median 36 µM, p<0.001, n = 30). In HIV-1 uninfected subjects, CD4+ lymphocytes were correlated with the combined factors α1PI, HLECS + lymphocytes, and CXCR4+ lymphocytes (r2 = 0.91, p<0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with >220 CD4 cells/µl, CD4+ lymphocytes were correlated solely with active α1PI (r2 = 0.93, p<0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human α1PI. Chimpanzee α1PI differs from human α1PI by a single amino acid within the 3F5-binding epitope. Unlike human α1PI, chimpanzee α1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4+ lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-α1PI immune complexes correlated with decreased CD4+ lymphocytes in HIV-1 subjects.ConclusionsThis report identifies an autoimmune component of HIV-1 disease that can be overcome therapeutically. Importantly, results identify an achievable vaccine modification with the novel objective to protect against AIDS as opposed to the current objective to protect against HIV-1 infection.

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Section: Introductionmentioning

confidence: 99%

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

et al. 2012

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“…Previous reports have demonstrated that inhibitory complexes formed between AAT and serine proteases decay with time and are dissociated in alkaline solutions ( 25 , 26 ). Thus, we tested WT SepA cleavage of AAT through a range of different pHs (pHs 5 to 9) or incubation times (from 0 to 60 min) but were unable to identify an inhibitory complex between AAT and SepA under any of the conditions tested ( Fig.…”

Section: Resultsmentioning

confidence: 99%

SepA EnhancesShigellaInvasion of Epithelial Cells by Degrading Alpha-1 Antitrypsin and Producing a Neutrophil Chemoattractant

Meza-Segura

Birtley

Maldonado‐Contreras

et al. 2021

mBio

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“…Thus it is an important regulator of trypsin-like extracellular serine proteases in vivo. Previous studies have shown that API can be proteolytically inactivated by various proteases such as papain, elastase, trypsin, and chymotrypsin [34][35][36] and by cleavage of the same peptide bond between 358-Met and 359-Ser [33,36]. Because it cleaves API, PSA may contribute to the regulation of the inhibitory activity of API in patients with advanced prostatic cancer and very high PSA levels in circulation.…”

Section: Discussionmentioning

confidence: 99%

Prostate-specific antigen forms a complex with and cleaves α1-protease inhibitor in vitro

et al. 1997

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The interaction of α1-antitrypsin with trypsin, chymotrypsin and human leukocyte elastase as revealed by end group analysis

Cited by 16 publications

References 39 publications

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

SepA EnhancesShigellaInvasion of Epithelial Cells by Degrading Alpha-1 Antitrypsin and Producing a Neutrophil Chemoattractant

Prostate-specific antigen forms a complex with and cleaves α1-protease inhibitor in vitro

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