Characterization of specific receptors for leukotriene D4 on human alveolar macrophages

Using ³H-leukotriene D₄, a specific receptor assay has been developed for human alveolar macrophages, obtained by broncho-alveolar lavage of patients undergoing fiberoptic bronchoscopy because of suspected bronchial carcinomaa. Lavage was performed in a carcinoma-free lobe of the lung and alveolar macrophages were subsequently isolated and incubated for binding studies. ³H-Leukotriene D₄ was found to bind specifically with high affinity (K_d = 3.8 nM), in a saturable manner (B_max = 90 fmol/10⁶ cells), reversible and selective. Specific binding was linear with protein concentration and equilibrium binding at 4°C was reached at 50 min. Scatchard and Hill analysis revealed a single class of binding sites with no cooperativity among the sites. displacement studies with LTD₄, the selective SRS-A antagonist FPL 55712 and with leukotriene C₄ revealed respective K_i values of 3.4; 16; and 110 nM. The data suggest that human alveolar macrophages may contain a specific receptor type for LTD₄, which has a relatively low affinity for LTC₄, and are discussed in relation to modulatory processes in the lung, apart from direct actions of LTD₄ on smooth muscle receptors. From the data here acquired, it may be apparent that the study of characteristics of receptors specific for a broncho-active substance like LTD₄ on huma alveolar macrophages, which play an important role in immuno-inflammatory processes seen in many chronic lung diseases, may yield major insights into the pathogenesis and therapy decisions involved in these diseases.