Expression and functional significance of an activation‐dependent epitope of the β1 integrins in chronic inflammatory diseases Article uri icon

abstract

  • The avidity of VLA integrins for their ligands can be increased by their transition to an active conformational state. This conformational change can be detected with a novel monoclonal antibody (mAb), termed 15/7, that recognizes an activation‐dependent conformational epitope on the common β1 polypeptide of different VLA αβ1 integrins. In an attempt to understand the possible role of the active conformational state of β1 integrins in vivo, we first investigated the expression of 15/7 epitope on T lymphocytes from patients with chronic inflammatory joint diseases. An enhanced expression of the 15/7 epitope was found in the synovial fluid (SF) T lymphocytes from these patients as compared to their peripheral blood (PB) T cells. The effect of different cytokines on the appearance of the 15/7 activation epitope in PB T lymphocytes was subsequently analyzed; interferon‐γ, interleukin‐2 and, to a lower extent, tumor necrosis factor‐α were able to induce an increased expression of the 15/7 epitope. This enhanced 15/7 expression correlated with a higher binding ability to fibronectin of cytokine‐activated T cells. The presence of this activation epitope was detected in a small proportion of T lymphocytes scattered within inflammatory foci of synovial membrane from rheumatoid arthritis and thyroid glands from Hashimoto%27s chronic thyroiditis. We then analyzed the possible role of 15/7 epitope expression on cell adhesion in vitro. Immunofluorescence studies showed that the 15/7 epitope displayed a spot‐like distribution, selectively decorating adhesive contacts of U‐937 myelomonocytic cells attached to the 80 kDa proteolytic fragment of fibronectin (FN80). Furthermore, the anti‐β1 15/7 mAb was able to induce both T lymphocyte, Jurkat and U‐937 cellular binding and spreading on FN80. Altogether these results indicate that an activated conformation of β1 integrins is detected in vivo in lymphocyte infiltrates from chronic inflammatory conditions. The active conformations of β1 integrins are regulated by physiologic mediators such as cytokines, play an important role in cellular attachment and spreading, and appear to be involved in the development of inflammatory processes. Copyright © 1995 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
  • The avidity of VLA integrins for their ligands can be increased by their transition to an active conformational state. This conformational change can be detected with a novel monoclonal antibody (mAb), termed 15/7, that recognizes an activation‐dependent conformational epitope on the common β1 polypeptide of different VLA αβ1 integrins. In an attempt to understand the possible role of the active conformational state of β1 integrins in vivo, we first investigated the expression of 15/7 epitope on T lymphocytes from patients with chronic inflammatory joint diseases. An enhanced expression of the 15/7 epitope was found in the synovial fluid (SF) T lymphocytes from these patients as compared to their peripheral blood (PB) T cells. The effect of different cytokines on the appearance of the 15/7 activation epitope in PB T lymphocytes was subsequently analyzed; interferon‐γ, interleukin‐2 and, to a lower extent, tumor necrosis factor‐α were able to induce an increased expression of the 15/7 epitope. This enhanced 15/7 expression correlated with a higher binding ability to fibronectin of cytokine‐activated T cells. The presence of this activation epitope was detected in a small proportion of T lymphocytes scattered within inflammatory foci of synovial membrane from rheumatoid arthritis and thyroid glands from Hashimoto's chronic thyroiditis. We then analyzed the possible role of 15/7 epitope expression on cell adhesion in vitro. Immunofluorescence studies showed that the 15/7 epitope displayed a spot‐like distribution, selectively decorating adhesive contacts of U‐937 myelomonocytic cells attached to the 80 kDa proteolytic fragment of fibronectin (FN80). Furthermore, the anti‐β1 15/7 mAb was able to induce both T lymphocyte, Jurkat and U‐937 cellular binding and spreading on FN80. Altogether these results indicate that an activated conformation of β1 integrins is detected in vivo in lymphocyte infiltrates from chronic inflammatory conditions. The active conformations of β1 integrins are regulated by physiologic mediators such as cytokines, play an important role in cellular attachment and spreading, and appear to be involved in the development of inflammatory processes. Copyright © 1995 WILEY‐VCH Verlag GmbH %26 Co. KGaA, Weinheim

publication date

  • 1995-01-01