Purification of a serine-proteinase inhibitor from human articular cartilage. Identity with the acid-stable proteinase inhibitor of mucous secretions

Böhm, Beate; Deutzmann, Rainer; Burkhardt, Harald

doi:10.1042/bj2740269

Cited by 24 publications

(7 citation statements)

References 29 publications

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“…Amino-terminal sequencing of the major purified inhibitor, obtained by this method revealed identity with the published N-terminal sequence of MPI inhibitors from epithelial secretions [18 ' 19] as well as with a recent report on the inhibitor from articular cartilage [9] . The second sequence (Fig.…”

Section: Discussionmentioning

confidence: 78%

A Comparative Study of the Low-Molecular Mass Serine. Proteinase Inhibitors of Human Connective Tissues

Andrews¹,

Melrose²,

Ghosh³

1992

Biological Chemistry Hoppe-Seyler

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Low molecular mass serine proteinase inhibitors isolated from human articular cartilage, intervertebral disc, meniscus, and costal cartilage were compared chromatographically. Similar charge and size properties were exhibited when these inhibitors were examined by gel permeation and cation exchange chromatography. The individual proteinase inhibitory species separated by these procedures all cross-reacted with a polyclonal antibody raised against the mucous proteinase inhibitors (MPIs) obtained from human bronchial secretions, however the distribution of these MPI-like species varied with the origin of the connective tissue. The major inhibitory species present in human articular cartilage and intervertebral disc were purified to homogeneity using gel filtration, cation exchange, trypsin affinity and high performance reverse phase chromatography. The amino-terminal sequences of the purified cartilage intervertebral disc inhibitors was found to be identical to the published sequence of MPIs isolated from parotid and seminal secretions. These findings indicate that the endogenous small molecular mass cationic serine proteinase inhibitory proteins present in human cartilaginous connective tissues are members of the MPI family of proteinase inhibitors.

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Section: Discussionmentioning

confidence: 78%

A Comparative Study of the Low-Molecular Mass Serine. Proteinase Inhibitors of Human Connective Tissues

Andrews¹,

Melrose²,

Ghosh³

1992

Biological Chemistry Hoppe-Seyler

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“…ALP circulates in blood, and experimental evidence indicates its physiologic expression by a variety of mucosal epithelial cells, by neutrophils (2), and by murine, but not human, macrophages (3). However, its low molecular weight (11 kd) and its cationic nature (pI Ͼ10) predispose ALP to leaving the circulation for specific accumulation in tissues, especially in cartilage (4,5).…”

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confidence: 99%

Antileukoproteinase: Modulation of neutrophil function and therapeutic effects on anti–type II collagen antibody–induced arthritis

Sehnert¹,

Cavcic²,

Böhm³

et al. 2004

Arthritis & Rheumatism

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Objective. Antileukoproteinase (ALP) is a physiologic inhibitor of granulocytic serine proteases. The present study was undertaken to investigate its therapeutic benefit in an antibody-transfer model of erosive polyarthritis and to elucidate its potential to interfere with immune complex-dependent inflammatory pathways.Methods. Arthritis development was induced in male (BALB/c ؋ B10.Q)F 1 mice by intravenous injection of two monoclonal antibodies specific for type II collagen and was quantified by clinical scoring and histopathology. Arthritis severity was assessed in a cohort of mice under systemic treatment with recombinant human ALP (daily doses of 0.1 mg for 5 days starting immediately after disease induction) in comparison with untreated controls. Concomitantly, functional assays (phagocytosis, oxidative burst, fluorescence-activated cell sorting analysis of integrin expression) were performed on neutrophils upon in vitro stimulation by IgG-coated latex beads.Results. ALP treatment reduced arthritis incidence and severity and had a protective effect against cartilage and bone erosion. ALP inhibited the conversion of the leukocyte ␤2 integrins into an active conformation upon Fc receptor stimulation of granulocytes. ALP bound to the actin-bundling protein L-plastin and down-modulated filamentous actin assembly in response to stimulation with IgG-coated latex beads in granulocytes. ALP exerted additional inhibitory effects on neutrophil functions associated with cytoskeletal reorganization, such as phagocytosis and oxidative burst.Conclusion. In addition to its antiprotease activity, ALP exerts a variety of blocking effects on neutrophil functions, probably due to modulation of cytoskeletal changes, that may contribute to this inhibitor's antiarthritis potential and qualify it as a multifunctional regulator of inflammatory responses.Antileukoproteinase (ALP), also named secretory leukocyte protease inhibitor for its presence in epithelial secretions and its ability to inhibit neutrophil serine protease, is a highly basic, acid-stable polypeptide. It comprises two mutually homologous highly disulfidebonded domains connected by a short linker (1). ALP circulates in blood, and experimental evidence indicates its physiologic expression by a variety of mucosal epithelial cells, by neutrophils (2), and by murine, but not human, macrophages (3). However, its low molecular weight (11 kd) and its cationic nature (pI Ͼ10) predispose ALP to leaving the circulation for specific accumulation in tissues, especially in cartilage (4,5).In addition to its antiproteolytic properties, ALP has been shown to exert a variety of antiinflammatory actions on macrophages and neutrophils (e.g., the suppression of lipopolysaccharide [LPS]-induced prostaglandin E 2 and matrix metalloproteinase production or

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“…In addition to tissue inhibitor of metalloproteinases, plasminogen activator inhibitor 1 is present in cartilage [13]. Another proteinase inhibitor, secretory leukocyte proteinase inhibitor was shown to be present in human articular cartilage [16].…”

Section: Catabolism Of Cartilagementioning

confidence: 99%

Chondroitin Sulphate for the Treatment of Osteoarthritis

Volpi

2005

CMCAIAA

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The aim of this review is to illustrate the structural biology and functions of chondroitin sulphate (CS) in the light of recent glycobiological studies suggesting its new fundamental biological functions, and to evaluate the literature on CS concerning the pathobiology of osteoarthritis (OA), to ascertain whether this agent should be classified as a symptomatic slow-acting drug (SYSADOA), a compound that has a slow onset of action in alleviating OA symptoms. A previous review [Volpi, N. The pathobiology of osteoarthritis and the rationale for the use of chondroitin sulfate for its treatment. Curr. Drug Targets Immune Endocr. Metabol. Disord., 2004, 4, 119] has been published on this topic and this article intends to extend and update CS data and its use in the treatment of OA.CS exhibits a wide range of biological activities and from a pharmacological point of view, it produces a slow but gradual reduction of the clinical symptoms of OA, and these benefits last for a long period after the end of treatment. Furthermore, many animal studies and clinical trials have proved the efficacy of CS as a structure-modifying OA drug agent able to reverse, retard, or stabilize the pathology of OA, thereby providing symptomatic relief in the long-term treatment. In addition, there are fewer side effects when compared with other drugs used to treat the symptoms of OA, as well as a lack of toxicity associated with long-term use of these agents. These properties are also related to the oral absorption of this molecule as high-molecular mass compounds having clusters of sulphate groups and high charge density, capable of exerting their chondroprotective activity in vivo.

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Purification of a serine-proteinase inhibitor from human articular cartilage. Identity with the acid-stable proteinase inhibitor of mucous secretions

Cited by 24 publications

References 29 publications

A Comparative Study of the Low-Molecular Mass Serine. Proteinase Inhibitors of Human Connective Tissues

A Comparative Study of the Low-Molecular Mass Serine. Proteinase Inhibitors of Human Connective Tissues

Antileukoproteinase: Modulation of neutrophil function and therapeutic effects on anti–type II collagen antibody–induced arthritis

Chondroitin Sulphate for the Treatment of Osteoarthritis

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