Manifestations of Cellular Immunity in the Rat After Prolonged Asbestos Inhalation

Abstract

Abstract A number of recent studies have suggested that the aleolar macrophage plays a crucial role in the development of asbestosis. In the current study the possible alterations of the cell-mediated immunologic mechanisms by asbestos-exposed macrophages were examined. Two inbred rat strains (BD-IX and AGUS) were exposed to UICC crocidolite asbestos by inhalation for extended periods. Alveolar macrophages and nylon column-purified T cell-enriched splenic lymphocytes were co-cultured (in both syngeneic and allogeneic situations) for 1 or 22 hr in vitro. Parallel studies were also performed on cell populations from control (nondusted) rats. After 1-hr culture significantly greater numbers of either syngeneic or allogeneic lymphocytes clustered around macrophages from dusted rats compared with control rats. After 22 hr culture. Sustained lymphocyte binding was observed only with co-cultures containing syngeneic lymphocytes and macrophages from dusted rats. A considerable number of allogeneic lymphocytes or lymphocytes from control rats were still attached to the dusted macrophages after 22 hr, however, and a similar effect could be produced by pretreatment of control macrophages with NaIO4. Sequential treatment of control macrophages with periodate and L-cysteine reduced the number of bound lymphocytes to those bound to untreated control macrophages. Pretreatment of the dusted macrophages with L-cysteine produced a sharp decline in the number of control lymphocytes or allogeneic dusted lymphocytes bound to the treated macrophage after 22 hr. Sustained lymphocyte-macrophage binding in co-cultures containing syngeneic lymphocytes and macrophages from dusted rats was not abolished by L-cysteine. Thus, two different mechanisms could explain the prolonged binding of dusted alveolar macrophages with T lymphocytes. One mechanism observed in co-cultures of dusted macrophages with control lymphocytes or allogeneic dusted lymphocytes was analogous to that produced by treatment of control macrophages with NaIO4, and could be abolished by L-cysteine. It is postulated that asbestos exposure may produce an effect on the alveolar macrophage membrane similar to peroxidation. Another mechanism was demonstrated in co-cultures of syngeneic dusted macrophages and dusted lymphocytes where the sustained clustering observed after 22 hr was not abolished by L-cysteine. This finding is consistent with a specific immune recognition of an asbestos-related macrophage-associated antigen. Both these alterations would be due to the inhalation of crocidolite asbestos over a prolonged period.