In vivo catabolism of heparin cofactor II and its complex with thrombin: Evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors

Pratt, Charlotte W.; Church, Frank C.; Pizzo, Salvatore V.

doi:10.1016/0003-9861(88)90173-7

Cited by 39 publications

(36 citation statements)

References 29 publications

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“…For example, cathepsin G, human neutrophil elastase, and thrombin, complexed with cognate serpins (␣ 1 -antichymotrypsin, AAT, and heparin cofactor II, respectively), are all cleared from the circulation of mice within minutes (15)(16)(17). Clearance of serpin-enzyme complexes is believed to be mediated via low-density lipoprotein receptor-related-protein-1 (LDLR1) in hepatocytes, which recognizes complexed but not uncomplexed serpins (18).…”

Section: Discussionmentioning

confidence: 99%

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Pemberton

Wright

Knight

et al. 2006

The Journal of Immunology

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The granule-derived mouse mast cell proteases-1 and -2 (mMCP-1 and -2) colocalize in similar quantities in mucosal mast cells but micrograms of mMCP-1 compared with nanograms of mMCP-2 are detected in peripheral blood during intestinal nematode infection. This differential systemic response was investigated both in vitro and in vivo. Bone marrow-derived mucosal mast cell homologs released similar quantities of mMCP-1 and-2 concomitantly with β-hexosaminidase in response to calcium ionophore (∼60% release) or IgE/DNP (25% release). In contrast, serum from mice sensitized by infection with Nippostrongylus brasiliensis 10 days earlier contained >1500-fold more mMCP-1 (10,130 ± 1,609 ng/ml) than mMCP-2 (6.4 ± 1 ng/ml), but, in gut lumen, the difference was ∼8-fold. After OVA sensitization, >600-fold more mMCP-1 (7,861 ± 2,209 ng/ml) than mMCP-2 (12.8 ± 4.7 ng/ml) was present in blood 1 h after challenge, but, in gut lumen, there were relatively comparable levels of mMCP-1 and -2. To estimate the rates of systemic accumulation and clearance, 10 μg of mMCP-1 or -2 was injected i.p. Plasma levels of injected mMCP-2 peaked (1%) at 15 min then declined, whereas levels of mMCP-1 were maximal (∼25%) at 3 h. Inactivation of mMCP-1 with PMSF before injection resulted in mMCP-2-like kinetics, but inhibition of mMCP-1 by serum gave kinetics similar to that of native mMCP-1. mMCP-1 isolated from serum is complexed with serpins and we conclude that both the accumulation and the longevity of mMCP-1 in blood is due to complex formation, protecting it from a pathway that rapidly clears mMCP-2, which is unable to form complexes with serpins.

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Section: Discussionmentioning

confidence: 99%

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Pemberton

Wright

Knight

et al. 2006

The Journal of Immunology

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“…Usually, such complexes are cleared from blood plasma with a half-life of a few minutes (Lollar and Owen, 1980;Fuchs et al, 1982;Gonias et al, 1982;Pizzo et al, 1988;Pratt et al, 1988;Mast et al, 1991; see also review by Andreasen et al, 1994). However, less is known about the molecular mechanisms of clearance.…”

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confidence: 99%

Specificity of Serine Proteinase/Serpin Complex Binding to Very‐Low‐Density Lipoprotein Receptor and α₂‐Macroglobulin Receptor/Low‐Density‐Lipoprotein‐Receptor‐Related Protein

Kasza

Petersen

Heegaard

et al. 1997

European Journal of Biochemistry

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Very-low-density lipoprotein receptor (VLDLR) and a,-macroglobulin receptorllow-density-lipoprotein-receptor-related protein (a,MFULRP) are multifunctional endocytosis receptors of the low-density lipoprotein receptor family. Both have been shown to mediate endocytosis and degradation of complex between plasminogen activators and type-1 plasminogen-activator inhibitor (PAI-1) by cultured cells. We have now studied the specificity of binding and endocytosis by VLDLR and a,MFULRP among a variety of serine proteinase/serpin complexes, including various combinations of the serine proteinases urokinasetype and tissue-type plasminogen aqtivators, plasmin, thrombin, human leukocyte elastase, cathepsin G, and plasma kallikrein with the serpins PAI-1, horse leukocyte elastase inhibitor, protein C inhibitor, C1-inhibitor, a,-antiplasmin, a,-proteinase inhibitor, a,-antichymotrypsin, protease nexin-1, heparin cofactor 11, and antithrombin 111. Binding was estimated with radiolabelled ligands in ligand blotting analysis and microtiter well assays. Endocytosis was estimated by measuring receptor-associated protein (RAP)-sensitive degradation of radiolabelled complexes by Chinese hamster ovary cells transfected with VLDLR cDNA and by COS-1 cells, which have a high endogenous expression of a,MR/LRP. We found that the receptors bind with high affinity to some, but not all, combinations of plasminogen activators and thrombin with PAI-1, protease nexin-I, protein C inhibitor, and antithrombin 111, while complexes of many serine proteinases with their primary inhibitor, i.e. plasmin/a,-antiplasmin complex, do not bind, or bind with a very low affinity. Both the serine proteinase and the serpin moieties contribute to the binding specificity. The binding specificities of VLDLR and a,MR/LRP are overlapping, but not identical. The results suggest that VLDLR and a,MR/LRP have different biological functions by having different binding specificities as well as by being expressed by different cell types.Keywords: low-density-lipoprotein-receptor-related protein; plasminogen activator; serine proteinase; serpin ; very-low-density lipoprotein receptor.A variety of physiological events, like blood coagulation, complement activation, fibrinolysis, and turnover of extracellular matrix, implicate the function of extracellular serine proteinase enzyme systems. Regulation of extracellular proteolysis caCorrespondence to P.

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“…API is able to inhibit several serine proteases, but the regulation of neutrophil elastase is considered to be its main physiological function (Beatty et al, 1980, Travis andSalvesen, 1983 Proteinases complexed to API can be degraded by other proteinases (Kaslik et al, 1995, Stavridi et al, 1996. This may be a faster way of proteinase elimination from the circulation than the SEC (serpinenzyme complex) receptor-based uptake and intracellular degradation of proteinase-API complexes (Perlmutter et al, 1990, Pizzo, 1989, Pratt et al, 1988. API inhibits trypsin-2 ten times faster than trypsin-1, and it has been suggested to control trypsin-1 activity in vivo when α 2 M is already saturated (VercaigneMarko et al, 1989).…”

Section: Trypsin Inhibitorsmentioning

confidence: 99%

Human trypsinogens in the pancreas and in cancer

Itkonen

2010

Scandinavian Journal of Clinical and Laboratory Investigation

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In vivo catabolism of heparin cofactor II and its complex with thrombin: Evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors

Cited by 39 publications

References 29 publications

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Specificity of Serine Proteinase/Serpin Complex Binding to Very‐Low‐Density Lipoprotein Receptor and α₂‐Macroglobulin Receptor/Low‐Density‐Lipoprotein‐Receptor‐Related Protein

Human trypsinogens in the pancreas and in cancer

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In vivo catabolism of heparin cofactor II and its complex with thrombin: Evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors

Cited by 39 publications

References 29 publications

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Anaphylactic Release of Mucosal Mast Cell Granule Proteases: Role of Serpins in the Differential Clearance of Mouse Mast Cell Proteases-1 and -2

Specificity of Serine Proteinase/Serpin Complex Binding to Very‐Low‐Density Lipoprotein Receptor and α2‐Macroglobulin Receptor/Low‐Density‐Lipoprotein‐Receptor‐Related Protein

Human trypsinogens in the pancreas and in cancer

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Specificity of Serine Proteinase/Serpin Complex Binding to Very‐Low‐Density Lipoprotein Receptor and α₂‐Macroglobulin Receptor/Low‐Density‐Lipoprotein‐Receptor‐Related Protein