The immune dysregulatory compound mercuric chloride induces integrin-mediated T-lymphocyte adhesion.
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 Mg2+ and Mn2+, can activate binding of integrins to their ligands, thus causing lymphocyte adhesion. To test the hypothesis that Hg2+ acts in a similar way, we studied the effect of HgCl2 on integrin-mediated T-cell adhesion. HgCl2 induced cell-cell aggregation of human T lymphoblasts. Exposure of a human T-cell clone to HgCl2 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, HgCl2 induced strong binding of Jurkat T cells to FN. These effects of HgCl2 were of similar magnitude as the effects of phorbol 12-myristate 13-acetate (PMA) or MnCl2. 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 HgCl2 or by PMA, but not by MnCl2, was dependent on temperature and on extracellular Ca2+ or Mg2+. Addition of cytochalasin B enhanced synergistically the FN adhesion induced by MnCl2, whereas the effects of PMA and HgCl2 were not modified. These results indicate that Hg2+ is a potent activator of T-cell adhesion, mediated by several integrins and ligands. In contrast to the effect of MnCl2, HgCl2-induced cell adhesion probably involves an intracellular pathway. Activation of integrins by HgCl2 may play an important role in activation and migration of leucocytes involved in HgCl2-induced immune dysregulation in vivo.
Roos
A
A
Department of Nephrology, Leiden University Medical Centre, Leiden, The Netherlands.
Neeft
M
M
Engelen
L
L
Schilder-Tol
E J
EJ
Kunzendorf
U
U
Weening
J J
JJ
Aten
J
J
D000199:Actins / Q000502:physiology; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques; D003599:Cytoskeleton / Q000276:immunology; D004202:Disinfectants / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D015636:Magnesium Chloride / Q000494:pharmacology; D008627:Mercuric Chloride / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D000199:Actins; D000891:Anti-Infective Agents, Local; D004202:Disinfectants; D016023:Integrins; D015636:Magnesium Chloride; D008627:Mercuric Chloride