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The immune dysregulatory compound mercuric chloride induces integrin‐mediated T‐lymphocyte adhesion
Author(s) -
Roos A.,
Neeft M.,
Engelen L.,
SchilderTol E. J. M.,
Kunzendorf U.,
Weening J. J.,
Aten J.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01160.x
Subject(s) - chemistry , integrin , cell adhesion , fibronectin , cell adhesion molecule , microbiology and biotechnology , t cell , jurkat cells , biochemistry , cell , immune system , immunology , biology
Summary Exposure of Brown Norway rats to mercuric chloride induces systemic autoimmunity, involving T‐ and B‐lymphocyte activation, (auto‐)antibody production and multiorgan inflammation. Several divalent metal ions, such as Mg 2+ and Mn 2+ , can activate binding of integrins to their ligands, thus causing lymphocyte adhesion. To test the hypothesis that Hg 2+ acts in a similar way, we studied the effect of HgCl 2 on integrin‐mediated T‐cell adhesion. HgCl 2 induced cell–cell aggregation of human T lymphoblasts. Exposure of a human T‐cell clone to HgCl 2 for 1 hr enhanced, in a dose‐dependent way, cell binding to fibronectin (FN) and to intercellular adhesion molecules (ICAM) ‐1, ‐2 and ‐3. Furthermore, HgCl 2 induced strong binding of Jurkat T cells to FN. These effects of HgCl 2 were of similar magnitude as the effects of phorbol 12‐myristate 13‐acetate (PMA) or MnCl 2 . Studies using blocking antibodies indicated the involvement of CD11a in binding to ICAMs, and of CD49d, CD49e, and CD29 in binding to FN. Adhesion to FN induced by HgCl 2 or by PMA, but not by MnCl 2 , was dependent on temperature and on extracellular Ca 2+ or Mg 2+ . Addition of cytochalasin B enhanced synergistically the FN adhesion induced by MnCl 2 , whereas the effects of PMA and HgCl 2 were not modified. These results indicate that Hg 2+ is a potent activator of T‐cell adhesion, mediated by several integrins and ligands. In contrast to the effect of MnCl 2 , HgCl 2 ‐induced cell adhesion probably involves an intracellular pathway. Activation of integrins by HgCl 2 may play an important role in activation and migration of leucocytes involved in HgCl 2 ‐induced immune dysregulation in vivo .