Influence of organophosphorus compounds on different cellular immune functions in vitro

Abstract

The effects of two organophosphorus compounds (OP) triphenyl phosphate (TPP) and triphenylphosphine oxide (TPPO) on different immune functions in vitro were investigated using an economical multiple endpoint approach. The test battery was designed as follows: immunocompetent cells (peritoneal cells and splenocytes) were isolated from female C57B1 mice and treated in vitro for 1 hr with the test article. Then the cells were washed and assessed for the following immune functions: Fc-receptor-dependent phagocytosis and lipopolysaccharide-induced release of a cytolytic protein (tumour necrosis factor, TNF) of thioglycollate-elicited peritoneal macrophages; natural killer (NK) cell activity, blastogenesis (T and B lymphocytes), and antibody synthesis (B lymphocytes) of spleen-cell suspensions. As an additional parameter the survival of the cells was determined routinely after treatment during all assays. No substantial effect on macrophage phagocytotic activity was observed after TPP or TPPO treatment. TPP led to a concentration-dependent suppression of macrophage TNF activity as well as NK activity of spleen cells. In addition, a slight reduction of B-lymphocyte antibody synthesis was obtained. TPPO treatment revealed a modulation of TNF activity of macrophages in a complex, non-concentration-related manner. A concentration-related suppression of spleen cell NK activity was observed after TPPO treatment. In summary, TPP and TPPO were found to be immunomodulating agents eliciting adverse effects predominantly towards cells of the innate immunity. The functions of T and B lymphocytes, referred to as adaptive immunity, were not substantially impaired. Our results indicate that the in vitro test battery described may be a suitable tool for the screening of OP-mediating immunotoxicity.