Characterization of substance P binding to human monocytes/macrophages

Substance P (SP), a member of the tachykinin family of neuropeptides, can immunomodulate human T cells and monocytes. SP has been shown to stimulate human monocytes to produce inflammatory cytokines and superoxide ions, and it enhances tumoricidal activity in vitro. A specific SP receptor, however, has not been identified on human monocytes/macrophages. In this study, we report that '251-SP binds to human monocytes/macrophages with high affinity and specificity (Kd = 2.7 x 10-8 to 5.5 x 10-8 M). Our measurements of binding affinity to this single class of receptors were possible only when experiments were performed in the presence of excess serine proteinase inhibitor (serpin) enzyme complex receptor ligand. We determined that 1251-SP bound to a specific receptor on human monocytes/macrophages and that this binding was detectable as early as 6 h and was maintained throughout 6 to 8 weeks in culture. Modulation of the diverse immunological and inflammatory effects of SP on human monocytes may be mediated through this specific SP receptor. Substance P (SP) is a member of the tachykinin family of neuropeptides (32). This 11-amino-acid peptide is a mediator in certain disease states through its influence on cells involved in inflammation and immune function (12, 22, 26). SP recep-tors have been detected on cells of the nervous system, vascula