Objective: To investigate the expression of granzyme B (GrB) in normal and rheumatoid arthritis (RA) articular cartilage, and to analyze the relationship between the expression of GrB and apoptotic chondrocytes in RA cartilage.
Methods: Normal cartilage samples were obtained from 9 resected joints and RA cartilage samples were obtained from 12 patients with RA during joint replacement surgery. Cartilage sections were analyzed by immunohistochemistry for the presence of GrB, and the mRNA expression of GrB in chondrocytes was analyzed by in situ hybridization and nonquantitative and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of perforin (PFN) was also assessed. Apoptotic chondrocytes were detected using TUNEL staining and their morphology was examined using electron microscopy.
Results: The immunohistochemical analyses revealed GrB and PFN expression in normal chondrocytes and a larger number of GrB and PFN-positive chondrocytes in RA cartilage. In situ hybridization and RT-PCR confirmed the expression of GrB and PFN mRNA, and semiquantitative RT-PCR showed elevated concentrations of GrB and PFN expression in RA chondrocytes. The distribution of GrB and PFN-positive cells in the RA cartilage samples was similar to that of apoptotic cells.
Conclusion: GrB and PFN expression is present in normal human articular chondrocytes and elevated in RA chondrocytes. The targets and precise functions of GrB expressed in chondrocytes remain to be determined, but GrB may be involved in the remodeling mechanism of matrix macromolecules and the endogenous degradation of RA cartilage.
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J Control Release
May 2024
Department of Medical Laboratory, School of Medical Technology, Tianjin Medical University, Tianjin 300203, China. Electronic address:
Granzyme B (GrB)-based immunotherapy is of interest for cancer treatment. However, insufficient cellular uptake and a lack of targeting remain challenges to make use of GrB for solid tumour therapy. As GrB induced cell death requires the help of perforin (PFN), we designed a system (nGPM) for the co-delivery of GrB and PFN.
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Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, 980-8575, Sendai, Japan,
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Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, Sendai, Japan.
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Department of Haematology and Oncology, Albert Ludwigs-University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
Cytotoxic T lymphocytes and natural killer cells (CTL/NK) induce cell death in leukemia cells by the granzyme B (grB)-dependent granule cytotoxin (GC) pathway. Resistance to GC may be involved in immune evasion of leukemia cells. The delivery of active grB into the cytoplasma is dependent on the presence of perforin (PFN) and grB complexes.
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