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 s timulate human monocytes to produce inflammatory cytokines and superox ide ions, and it enhances tumoricidal activity in vitro. A specific SP receptor, however, has not been identified on human monocytes/macroph ages. In this study, we report that I-125-Sp binds to human monocytes/ macrophages with high affinity and specificity (K-d = 2.7 x 10(-8) to 5.5 x 10(-8) M). Our measurements of binding affinity to this single c lass of receptors were possible only when experiments were performed i n the presence of excess serine proteinase inhibitor (serpin) enzyme c omplex receptor ligand. We determined that I-125-Sp bound to a specifi c receptor on human monocytes/macrophages and that this binding was de tectable as early as 6 h and was maintained throughout 6 to 8 weeks in culture. Modulation of the diverse immunological and inflammatory eff ects of SP on human monocytes may be mediated through this specific SP receptor.