OBJECTIVE: To examine the gene expression of 2 highly specific markers of cytotoxic T lymphocyte (CTL) activation, the serine protease granzyme A and the pore-forming protein perforin, in synovial tissue of patients with rheumatoid arthritis (RA), and to compare the findings with those in osteoarthritis (OA) synovial tissue. METHODS: Snap-frozen synovial tissue specimens from 9 patients with RA and 5 patients with OA were examined. The number of CTL that expressed granzyme A or perforin messenger RNA was determined by in situ hybridization using nonradioactive riboprobes for granzyme A and perforin, and by a novel in situ reverse transcriptase technique. The signals were visualized by an immunogold-silver immunohistochemistry technique and compared with immunohistochemical labeling of T and B cells. Additional double-labeling was achieved using anti-type IV collagen, anti-macrophage (anti-CD68), anti-T lymphocyte (anti-CD45RO), anti-B lymphocyte (anti-CD20), and anti-natural killer cell (anti-CD56) antibodies in an alkaline phosphatase-anti-alkaline phosphatase assay. RESULTS: Granzyme A and perforin messenger RNA (mRNA) was observed in CTL in synovial specimens from all of the RA patients, whereas in specimens from OA patients only a few, single cells with a positive mRNA signal for these molecules could be detected. In the RA specimens, the number of lymphocytes showing a positive mRNA signal for granzyme A or perforin varied from 10% to 50%, reflecting the recent findings of other investigators studying synovial fluid. CONCLUSION: Our results demonstrate that gene expression of at least 2 CTL products, granzyme A and perforin, is up-regulated in the synovium of patients with RA compared with that in the synovium of patients with OA. These molecules presumably play an important role not only in lymphocyte-mediated cytotoxicity, but also in facilitating the migration of blood-borne mononuclear cells through the vascular basement membrane into the rheumatoid synovium.
OBJECTIVE: To examine the gene expression of 2 highly specific markers of cytotoxic T lymphocyte (CTL) activation, the serine protease granzyme A and the pore-forming protein perforin, in synovial tissue of patients with rheumatoid arthritis (RA), and to compare the findings with those in osteoarthritis (OA) synovial tissue. METHODS: Snap-frozen synovial tissue specimens from 9 patients with RA and 5 patients with OA were examined. The number of CTL that expressed granzyme A or perforin messenger RNA was determined by in situ hybridization using nonradioactive riboprobes for granzyme A and perforin, and by a novel in situ reverse transcriptase technique. The signals were visualized by an immunogold-silver immunohistochemistry technique and compared with immunohistochemical labeling of T and B cells. Additional double-labeling was achieved using anti-type IV collagen, anti-macrophage (anti-CD68), anti-T lymphocyte (anti-CD45RO), anti-B lymphocyte (anti-CD20), and anti-natural killer cell (anti-CD56) antibodies in an alkaline phosphatase-anti-alkaline phosphatase assay. RESULTS:Granzyme A and perforin messenger RNA (mRNA) was observed in CTL in synovial specimens from all of the RApatients, whereas in specimens from OA patients only a few, single cells with a positive mRNA signal for these molecules could be detected. In the RA specimens, the number of lymphocytes showing a positive mRNA signal for granzyme A or perforin varied from 10% to 50%, reflecting the recent findings of other investigators studying synovial fluid. CONCLUSION: Our results demonstrate that gene expression of at least 2 CTL products, granzyme A and perforin, is up-regulated in the synovium of patients with RA compared with that in the synovium of patients with OA. These molecules presumably play an important role not only in lymphocyte-mediated cytotoxicity, but also in facilitating the migration of blood-borne mononuclear cells through the vascular basement membrane into the rheumatoid synovium.
Authors: Yubo Sun; David R Mauerhan; Gary S Firestein; Bryan J Loeffler; Edward N Hanley; Helen E Gruber Journal: J Rheumatol Date: 2009-01 Impact factor: 4.666
Authors: C Xue; M Takahashi; T Hasunuma; H Aono; K Yamamoto; S Yoshino; T Sumida; K Nishioka Journal: Ann Rheum Dis Date: 1997-04 Impact factor: 19.103
Authors: Fernando Pereira Carlos; Marcelo de Paula Alves da Silva; Eliadna de Lemos Vasconcelos Silva Melo; Maricilia Silva Costa; Stella Regina Zamuner Journal: Lasers Med Sci Date: 2013-08-10 Impact factor: 3.161
Authors: Yubo Sun; David R Mauerhan; Atiya M Franklin; James Norton; Edward N Hanley; Helen E Gruber Journal: Biomed Res Int Date: 2013-02-21 Impact factor: 3.411