Altered Storage of Proteases in Mast Cells from Mice Lacking Heparin: A Possible Role for Heparin Carboxypeptidase A Processing
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Frida Henningsson
Abstract
Heparindeficient mice, generated by gene targeting of Ndeacetylase/Nsulfotransferase-2 (NDST-2), display severe mast cell defects, including an absence of stored mast cell proteases. However, the mechanism behind these observations is not clear. Here we show that NDST-2+/+ bone marrowderived mast cells cultured in the presence of IL-3 synthesise, in addition to highly sulphated chondroitin sulphate (CS), small amounts of equally highly sulphated heparinlike polysaccharide. The corresponding NDST-2/ cells produced highly sulphated CS only. Carboxypeptidase A (CPA) activity was detected in NDST+/+ cells but was almost absent in the NDST/ cells, whereas tryptase (mouse mast cell protease 6; mMCP-6) activity and antigen was detected in both cell types. Antigen for the chymase mMCP-5 was detected in NDST-2+/+ cells but not in the heparindeficient cells. Northern blot analysis revealed mRNA expression of CPA, mMCP-5 and mMCP-6 in both wildtype and NDST-2/ cells. A ~36 kDa CPA band, corresponding to proteolytically processed active CPA, as well as a ~50 kDa proCPA band was present in NDST-2+/+ cells. The NDST-2/ mast cells contained similar levels of proCPA as the wildtype mast cells, but the ~36 kDa band was totally absent. This indicates that the processing of proCPA to its active form may require the presence of heparin and provides the first insight into a mechanism by which the absence of heparin may cause disturbed secretory granule organisation in mast cells.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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- Thyroid Stimulating Hormone Upregulates Secretion of Cathepsin B from Thyroid Epithelial Cells
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- Spin Adducts of Superoxide, Alkoxyl, and Lipid-Derived Radicals with EMPO and Its Derivatives
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- Analysis of the Structural Determinants for RNA Binding of the Human Protein AUF1/hnRNP D
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- Stage-Specific Antimalarial Activity of Cysteine Protease Inhibitors
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- Design of Inhibitors for Human Tissue Kallikrein Using Non-Natural Aromatic and Basic Amino Acids
- Amyloid Fibril Formation by Human Stefin B in vitro: Immunogold Labelling and Comparison to Stefin A
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Articles in the same Issue
- Nobuhiko Katunuma: An Outstanding Scientific and Professional Career of a Warm-Hearted Person. Reflections on the Occasion of his 75th Birthday
- Structural and Functional Diversity of Connexin Genes in the Mouse and Human Genome
- Congopain from Trypanosoma congolense: Drug Target and Vaccine Candidate
- Biosynthesis of Lysosomal Proteinases in Health and Disease
- Calpain Function in the Differentiation of Mesenchymal Stem Cells
- Ku Antigen Supports Termination of Mammalian rDNA Replication by Transcription Termination Factor TTF-I
- Thyroid Stimulating Hormone Upregulates Secretion of Cathepsin B from Thyroid Epithelial Cells
- Selective Release of Calpain Produced αII-Spectrin (α-Fodrin) Breakdown Products by Acute Neuronal Cell Death
- Altered Storage of Proteases in Mast Cells from Mice Lacking Heparin: A Possible Role for Heparin Carboxypeptidase A Processing
- Clustering-Induced Signaling of CEACAM1 in PC12 Cells
- Spin Adducts of Superoxide, Alkoxyl, and Lipid-Derived Radicals with EMPO and Its Derivatives
- Glutathione S-Transferase of the Malarial Parasite Plasmodium falciparum: Characterization of a Potential Drug Target
- Analysis of the Structural Determinants for RNA Binding of the Human Protein AUF1/hnRNP D
- Effect of Cysteine Proteinase Inhibitors on Murine B16 Melanoma Cell Invasion in vitro
- Stage-Specific Antimalarial Activity of Cysteine Protease Inhibitors
- Epoxysuccinyl Peptide-Derived Cathepsin B Inhibitors: Modulating Membrane Permeability by Conjugation with the C-Terminal Heptapeptide Segment of Penetratin
- Design of Inhibitors for Human Tissue Kallikrein Using Non-Natural Aromatic and Basic Amino Acids
- Amyloid Fibril Formation by Human Stefin B in vitro: Immunogold Labelling and Comparison to Stefin A
- Lysosomal Peptidases and Glycosidases in Rheumatoid Arthritis
