Trimellitic anhydride-induced allergic response in the guinea pig lung involves antibody-dependent and -independent complement system activation

Trimellitic anhydride (TMA) is one of many low molecular weight compounds k nown to cause occupational asthma. In our previous studies the TMA-induced allergic response in guinea pigs was attenuated by depletion of complement. Specifically, the leakage of red blood cells and infiltration of inflammat ory cells into the lung after TMA challenge was significantly reduced. Thus , we hypothesize that in the presence of specific antibody, TMA activates t he complement system and complement activation products play a role in medi ating inflammatory cell infiltration into the lung and lung hemorrhage. Gui nea pigs were sensitized by intradermal injection of TMA in corn oil. An in crease in the complement activation product C3a was detected in bronchoalve olar lavage, but not in plasma, of both sensitized and nonsensitized guinea pigs after intratracheal challenge with TMA conjugated to GPSA (TMA-GPSA). In vitro experiments demonstrated that TMA-GPSA caused complement activati on by antibody-dependent as well as antibody-independent pathways. In sensi tized animals, TMA-GPSA challenge caused significant increases in eosinophi ls, neutrophils, and macrophages in lung, along with increases in red blood cells and protein in the airspace. The infiltration of eosinophils was uni que in that the magnitude of the GPSA/TMA-GPSA effect was significantly dif ferent between nonsensitized and sensitized animals. C3a concentrations in BAL correlated with all measures of cell infiltration in sensitized animals , but not in nonsensitized animals. These data indicate that complement act ivation in the absence of antibody is not sufficient for the complete aller gic response to occur. Both sensitization and the complement system are req uired for TMA-induced eosinophilia.