Interaction between α1 antitrypsin and lymphocyte surface proteases: immunoregulatory effects

Bata, Jacqueline; Revillard, Jean‐Pierre

doi:10.1007/bf01978764

Cited by 17 publications

(8 citation statements)

References 18 publications

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“…Both α 1 -PI and α 2 -macroglobulin binding to lymphocyte surface proteases downregulate immune reaction of lymphoid cells (45)(46)(47). Both α 1 -PI and α 2 -macroglobulin binding to lymphocyte surface proteases downregulate immune reaction of lymphoid cells (45)(46)(47).…”

Section: Immunoregulatory Function Of Taurine Chloraminementioning

confidence: 99%

Myeloperoxidase-mediated Protein Oxidation: Its Possible Biological Functions

Naskalski¹,

Marcinkiewicz²,

Drożdż³

2002

Clinical Chemistry and Laboratory Medicine

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Oxidation of proteins occurs both as a side-effect of aerobic energy metabolism and as an effect of specific metabolism of phagocytic polymorphonuclear granulocytes producing O2- and H2O2. In contrast to other cells, which control their H2O2 level by degrading it to O2 and H2O, polymorphonuclear neutrophilic leukocytes (PMN) use H2O2 as a substrate for oxidizing chloride ions to HOCl which rapidly react with all neighboring thiol, disulfide and amino residues. Chloramines, which are the most abundant HOCl reaction products, react with proteins, modifying only certain exposed methionine and cysteine residues. This may account for selective inactivation of a number of enzymes, carrier proteins and peptide mediators, including the alpha1-proteinase inhibitor, alpha2-macroglobulin and plasminogen activator inhibitor. Inactivaton of plasma proteinase inhibitors protects PMN elastase, collagenase, cathepsin G and other serine proteases in the inflammatory foci. This promotes proteolytic degradation of damaged tissue, removal of bacterial debris and wound healing, as well as tissue remodeling related to the inflammatory processes. Oxidative control of protease-anti-protease balance affects the development of the inflammatory processes. Moreover, inactivation of plasma proteinase inhibitors facilitates primary antigen processing, upregulates lymphocyte proliferative response and activates the local immune response. Oxidation produces a specific protein tagging which attracts and stimulates immune active cells. Therefore, humoral response against oxidatively modified proteins occurs more effectively than that of the native proteins. The effect is dose-dependent with respect to the amount of oxidant employed. Glycol aldehyde, which is the serine chloramine spontaneous decay product, in mice immunized with glycol aldehyde-modified egg-white albumin, yields specific IgG production manifold higher than that in mice immunized with native albumin. Immunopotentiation is produced by proliferation expansion of the same immunocompetent clones. Oxidative tagging of proteins may also affect the autoimmune-type reaction. Thus, a growing body of data suggest that the specific role of protein oxidation by activated PMN is oxidative protein tagging facilitating further development of the immune reaction.

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Section: Immunoregulatory Function Of Taurine Chloraminementioning

confidence: 99%

Myeloperoxidase-mediated Protein Oxidation: Its Possible Biological Functions

Naskalski¹,

Marcinkiewicz²,

Drożdż³

2002

Clinical Chemistry and Laboratory Medicine

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“…8] and lympho cytes [5,6,9], The potential importance of membrane-bound peptidases and proteases as critical regulators of intercellular communica tion is now largely accepted. Activated pro teases of T and B lymphocytes are involved in cell killing and lymphocyte function [10][11][12], Moreover, synthetic and natural inhibitors of these enzymes modify the immune response [13][14][15], Finally, increased protease activity may mediate angiogenesis and tumor growth [16,17], Intercellular communication plays a major role in the development of glomerulo nephritis because glomeruli contain both resi dent cells of three different types and bloodborne cells including macrophages which in teract with each other. In particular, mesangial cells are the source and the target of a variety of autacoids.…”

Section: Introductionmentioning

confidence: 99%

Characterization and Control of Expression of Cell Surface Aminopeptidase N Activity in Human Mesangial Glomerular Cells

Stefanović¹,

Vlahović²,

Ardaillou³

et al. 1992

Cell Physiol Biochem

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Intact human glomerular mesangial cells in culture hydrolyzed synthetic substrates of aminopeptidase N. Mesangial cell aminopeptidase N is an ectoenzyme as demonstrated by the extracellular location of the product, the inhibition of enzyme activity by the diazonium salt of sulfanilic acid, a nonpenetrating agent, the similar activities measured with intact and sonicated cells and the localization of the immunoreactive antigen by immunofluorescence on the cell surface. A broad substrate specificity was documented with various p-nitroanilide substrates in the following order of affinity: Ala, Leu > Lys, Arg > Pro, Gly and Val. Using Ala p-nitroanilide as substrate, apparent K_m and V_max values of 0.86 ± 0.70 mM and 3.54 ± 0.13 nmol min^–1 mg^–1, respectively were obtained. Enzyme activity was inhibited by bestatin and 1, 10-phenanthroline. Inhibition by 1 10-phenanthroline was noncompetitive. Cell surface aminopeptidase N activity increased in the presence of phorbolmyristate acetate (PMA). This effect was time-dependent, requiring a lag time of 12 h. It was also concentration-dependent with a threshold at 1 ng/ml and a maximum stimulation (2.2 times basal value) at 10 ng/ml. The effect of PMA was prevented by cycloheximide, an inhibitor of protein synthesis, and actinomycin D, an inhibitor of RNA synthesis. It was also suppressed by H7, an inhibitor of protein kinase C activity. The presence of aminopeptidase N in cultured glomerular mesangial cells and control of its expression by mitogens suggest that this enzyme may play a role in glomerular cell proliferation.

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“…It was reported more than 25 years ago that AAT bound to lymphocyte membranes, inhibited their surface proteases, and altered monocyte‐lymphocyte interactions 24. Many effects of AAT may involve inhibition of proteases produced by 1 cell that act on adjacent cells and/or inhibition of protease‐activated receptors.…”

Section: Novel Functions Of Aatmentioning

confidence: 99%

“…Many effects of AAT may involve inhibition of proteases produced by 1 cell that act on adjacent cells and/or inhibition of protease‐activated receptors. Together with intracellular effects, these membrane effects likely contribute to a net decrease in cytokines that favor sensitization, such as IL‐1, TNFα, IL‐6, and IL‐32, while promoting tolerance by preserving transforming growth factor‐β and increasing IL‐10 and IL‐1 receptor antagonist 4, 6, 7, 24, 25, 26, 27, 28. These effects likely contribute to the induction of regulatory T cells (Tregs) that promote allograft survival 6, 7, 9, 25, 26, 27, 28.…”

Section: Novel Functions Of Aatmentioning

confidence: 99%

“…It was reported more than 25 years ago that AAT bound to lymphocyte membranes, inhibited their surface proteases, and altered monocyte-lymphocyte interactions. 24 Many effects of AAT may involve inhibition of proteases produced by 1 cell that act on adjacent cells and/or inhibition of protease-activated receptors. Together with intracellular effects, these membrane effects likely contribute to a net decrease in cytokines that favor sensitization, such as IL-1, TNFα, IL-6, and IL-32, while promoting tolerance by preserving transforming growth factorβ and increasing IL-10 and IL-1 receptor antagonist.…”

Section: Effects On Lymphocytesmentioning

confidence: 99%

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Alpha-1-antitrypsin in cell and organ transplantation

Berger

Liu

Uknis

et al. 2018

American Journal of Transplantation

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Limited availability of donor organs and risk of ischemia‐reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha‐1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor that limits inflammatory tissue damage. Purified plasma–derived AAT has been well tolerated in more than 30 years of use to prevent emphysema in AAT‐deficient individuals. Accumulating evidence suggests that AAT has additional anti‐inflammatory and tissue‐protective effects including improving mitochondrial membrane stability, inhibiting apoptosis, inhibiting nuclear factor kappa B activation, modulating pro‐ vs anti‐inflammatory cytokine balance, and promoting immunologic tolerance. Cell culture and animal studies have shown that AAT limits tissue injury and promotes cell and tissue survival. AAT can promote tolerance in animal models by downregulating early inflammation and favoring induction and stabilization of regulatory T cells. The diverse intracellular and immune‐modulatory effects of AAT and its well‐established tolerability in patients suggest that it might be useful in transplantation. Clinical trials, planned and/or in progress, should help determine whether the promise of the animal and cellular studies will be fulfilled by improving outcomes in human organ transplantation.

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Interaction between α1 antitrypsin and lymphocyte surface proteases: immunoregulatory effects

Cited by 17 publications

References 18 publications

Myeloperoxidase-mediated Protein Oxidation: Its Possible Biological Functions

Myeloperoxidase-mediated Protein Oxidation: Its Possible Biological Functions

Characterization and Control of Expression of Cell Surface Aminopeptidase N Activity in Human Mesangial Glomerular Cells

Alpha-1-antitrypsin in cell and organ transplantation

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