Keynote lecture in the 13th Japanese Society of Immunotoxicology (JSIT 2006)

Abstract

Silica and silicates may disturb immune functions such as autoimmunity and tumor immunity, because people who are exposed to the materials sometimes develop autoimmune and malignant diseases, respectively. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer in 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate the nation wide anxiety about these malignancies.

Soluble Interleukin-2 Receptor as an Indicator of Immunological Disturbance Found in Silicosis Patients

“…Our previous study showed that the CD4+25+Treg fraction derived from SILs possess impaired regulatory function (24). This reduction in the Treg fraction may be involved in the genesis of autoimmune disturbance found in SILs (8)(9)(10).…”

“…We previously reported on the cellular and molecular changes associated with Fas and Fasrelated molecules in SILs and healthy donors (HD) (8)(9)(10). Fas is considered to be critical for apoptotic events in immunocompetent cells, such as T cells, and the impairment of Fas through mutation results in excessive autoreaction which causes lymphoproliferative lymphoadenopathy and the occurrence of autoimmune disorders due to the unexpected long-term survival of self-recognizing T cell clones (11).…”

“…Conditions associated with the expression of abnormal Fas or Fas-related molecules include (i) elevated levels of serum-soluble Fas (sFas) in SILs, (ii) excessive expression of soluble rather than wildtype Fas genes in peripheral blood mononuclear cells (PBMCs) from SILs, (iii) excessive detection of variant messages of Fas transcripts as well as sFas, (iv) excessive expression of decoy receptor 3 (DcR3) in PBMCs from SILs, (v) reduced expression of intracellular anti-apoptotic molecules related to Fas-mediated apoptosis in PBMCs from SILs, and (vi) the detection of functional (apoptosis inducible) serum anti-Fas autoantibody in SILs (8)(9)(10)(12)(13)(14)(15)(16). These Fas-related parameters were isolated as immunological parameters from other respiratory clinical parameters such as percent vital capacity (%VC), profusion rate (PR), which is a category pertaining to radiological findings according to the International Labor Office (ILO) guideline (17), and the percentage of forced expiratory volume in 1 second (FEVl.O%) (18).…”