IgE-dependent activation of alveolar macrophages augments neurally mediated contraction of small airways

Abstract

1. We studied the effect of immunologically activated pulmonary alveolar macrophages (PAM) on functions of canine bronchiolar smooth muscle under isometric conditions in vitro. 2. PAM, stimulated with monoclonal anti-dinitrophenyl (DNP) IgE antibody and DNP-human serum albumin (DNP-HSA), augmented the contractile responses of bronchioles to electrical field stimulation, whereas PAM treated with IgE antibody alone had no effect. 3. In contrast, the contractile responses to exogenously administered acetylcholine were not influenced by immunologically activated PAM. 4. The PAM-induced increase in the contractile responses to field stimulation was inhibited by pretreatment of PAM with indomethacin and by addition of the thromboxane A2 (TxA2) receptor antagonist SQ 29548. 5. The release of TxA2 from PAM was increased by anti-DNP IgE and DNP-HSA, an effect that was prevented by indomethacin. 6. These results suggest that PAM may play a role in the development of antigen-induced hyperreactivity of small airways through an IgE-dependent release of TxA2 which potentiates prejunctionally the parasympathetic component of bronchiolar smooth muscle tone.