%0 Journal Article
%T Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages in vitro
%A Dingena L Valstar
%A Marcel A Schijf
%A Erietta Stelekati
%A Frans P Nijkamp
%A Nanne Bloksma
%A Paul AJ Henricks
%J Journal of Occupational Medicine and Toxicology
%D 2006
%I BioMed Central
%R 10.1186/1745-6673-1-13
%X Cells were incubated with different concentrations of TMA, TMA conjugated to bovine serum albumin (BSA), and BSA as a control for 24 h and the culture supernatant was analyzed for mediator content.TMA alone was not able to induce the production of mediators by NR8383 cells and primary AMs from sensitized and sham-treated rats. TMA-BSA, on the contrary, dose-dependently stimulated the production of NO, TNF, and IL-6 by NR8383 cells and of NO and TNF, but not IL-6, by primary AMs independent of sensitization.Results suggest that although TMA is a highly reactive compound, conjugation to a suitable protein is necessary to induce mediator production by AMs. Furthermore, the observation that effects of TMA-BSA were independent of sensitization suggests involvement of an immunologically non-specific receptor. In the discussion it is argued that a macrophage scavenger receptor is a likely candidate.Trimellitic anhydride (TMA) is a reactive low molecular weight (LMW) chemical used in the manufacture of paints, epoxy curing agents, printing inks and vinyl plasticizers and is known to cause occupational asthma characterized by airflow obstruction, airway inflammation and non-specific bronchial hyperreactivity [1-3]. The development of this allergic disease requires sensitization triggered by dermal or respiratory exposure to TMA followed by its binding to proteins [4]. These so formed TMA-protein conjugates will then be taken up by antigen-presenting cells, transported to the regional lymph node, and presented to TMA-specific T cells resulting in T cell memory and the production of TMA-specific IgE antibodies. These antibodies will then bind to the high-affinity IgE receptor on mast cells [5,6] and upon renewed contact with TMA mediate cross-linking of the IgE-receptors with subsequent release of mediators, that in their turn cause bronchoconstriction and attraction of inflammatory cells [7-9].Alveolar macrophages (AMs) are among the first cells that encounter inhaled small p
%U http://www.occup-med.com/content/1/1/13