2-Hydroxyethylmethacacrylate. Effects on the immune system in mice

Abstract

The use of acrylic compounds in dentistry has increased. Different derivatives of acrylic acid are used in dental bonding material, in resins and in glass ionomer cements. While there have been only a few reports on adverse reactions in patients, there is substantial evidence of adverse reactions in dental personnel. Both irritant and allergic contact dermatitis (ICD and ACD) have been reported as well as airway hyper responsiveness. Low molecular weight compounds, like acrylic substances, are too small to be discerned by the immune system on their own. In order for them to cause ACD, a prerequisite is their binding to endogenous protein in the epidermis. Eventually this will lead to the activation of T cells, committed to the modification caused by the chemical, and to an inflammatory response in the skin. A possible consequence of the binding of the monomer to a self protein could be the activation of B cells specific for unmodified parts of the carrier. This thesis has sought to investigate effects on the immune system of one acrylic monomer: 2-Hydroxyethylmethacrylate (HEMA). The central point has been to elucidate possible consequences on B cell responses induced by exposure to a chemically modified self-protein. The influence of some physical parameters on the tendency of HEMA to bind to proteins was studied. This was done by titrating the number of free lysine residues in bovine serum albumin subsequent to its incubation with HEMA. The effect on B cells by HEMA modified endogenous proteins was studied in a mouse model i.e. mouse serum albumin (MSA) was conjugated to different degrees with HEMA. Female Balb/c mice were then immunized with these preparations and the anti-MSA antibody response was analyzed by ELISA. The adjuvant capacity of HEMA was studied by co-administration of HEMA with a protein antigen. In order to investigate the penetration of HEMA through skin, mice were painted on the dorsum of their ears with the substance. HEMA binds to protein at physiological pH and the reaction rate is promoted by a raise in pH. The conjugation degree is also influenced by temperature and concentration of HEMA and protein. Auto-antibodies to MSA develop in mice that are immunized with HEMA-conjugated MSA. The antibody activity is dependent on the conjugation degree. Thus, a significantly higher activity is induced by a low degree of conjugation of the carrier protein, i.e. above a threshold ratio, as compared to higher conjugation degrees. Co-administration of unconjugated HEMA with a foreign protein antigen increases the antibody response to the protein significantly. This study has shown that HEMA, commonly used in dental practice and considered as a weak sensitizer in humans, possesses qualities associated with substances suspected to be allergenic: It can bind to protein and it has adjuvant properties. The induction of autoantibodies to a HEMA conjugated self-protein in mice warrants further investigations in humans exposed to HEMA.